Repetitive Transcranial Magnetic Stimulation (rTMS)

Dans notre centre de Neurologie à Gland, nous avons maintenant la possibilité d’effectuer des traitements de stimulation magnétique transcrânienne répétitive (rTMS).

Nous sommes les seuls neurologues installés, de la Suisse romande à proposer ce traitement ambulatoire.

Il s’agit d’une méthode non invasive de stimulation magnétique directe du cortex cérébral (environ 2000-3000 stimulations par séance). En fonction de la fréquence de stimulation, il est possible d’obtenir un effet d’excitation ou d’inhibition sur le cerveau. Par exemple si l’on stimule la région motrice de la main de la région prérolandique, la main controlatérale à la stimulation bouge. L’efficacité thérapeutique de la rTMS est désormais reconnue par un grand nombre d’études scientifiques dans le cas de certaines maladies neurologiques et psychiatriques. Ces études ont permis de définir des protocoles paramétrés de rTMS (nombre de stimuli, intensité et fréquence de stimulation) et de définir les régions cérébrales cibles. Les régions de stimulation sont localisées sur le crâne sur la base d’algorithmes standard.

La rTMS n’a pratiquement pas ou presque pas d’effets secondaires. Le traitement est ambulatoire et il n’y a aucune sédation ou anesthésie qui est nécessaire.     Ce traitement est néanmoins contre-indiqué chez les personnes porteuses d’implants cochléaires, pace makers et défibrillateurs cardiaques, ainsi que les patients épileptiques.
Les effets positifs du traitement apparaissent en général après 2-3 semaines de traitement.

La rTMS est indiqué comme thérapie pour les douleurs neurogènes d’origine centrale, la migraine chronique et autres conditions douloureuses par exemple la fibromyalgie

L’héminegligence spatiale et l’aphasie après accident vasculaire pourraient aussi bénéficier de la rTMS dans la phase de récupération.
L’efficacité a été démontrée dans les cas de la dépression résistante et des hallucinations auditivo-verbales non-répondantes aux traitements pharmacologiques. La rTMS pourrait être considérée aussi pour les patients (avec une dépression endogène), qui refusent un traitement pharmacologique.
Parmi d’autres conditions pour lesquels le traitement de rTMS peut être considéré, il y a aussi les acouphènes et les troubles anxieux. Pour les pathologies psychiatriques l’indication doit être discutée obligatoirement avec le médecin psychiatre référent du patient. Pour la fibromyalgie l’indication doit être discutée avec le rhumatologue référent du patient.

Nous sommes naturellement à votre disposition pour discuter de chaque patient les indications et le protocole de la rTMS.

Dr Antonio Carota et Dr André Menétrey

Pour d’autres informations, il faut visiter

http://tms-therapie.ch/fr/


 

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Dysprosody

The prosody is a communicative linguistic function, which results from the intonation, cadence, accent, and physical duration of the words. The prosody enhances the comprehension or the composed words, the basic emotions (rage, fear, sadness, surprise, disgust, pleasure), the subtle emotional aspects of the discourse (irony, sarcasm, deception, boredom, solace), and allows the differentiation of declarative, interrogative, and imperative phrases.

Thus, the expressive (affective) dysprosody is a suprasegmental deficit of language which should not be explained by a motor (dysarthria) or premotor (language apraxia) deficit, nor phonological or aphasic dysfunction (such as agrammatism and anomia). The patients with receptive dysprosody do not understand the emotional information of the phrases or the meaning of gesticulation.

Affective dysprosody could be an early predictor of post-stroke depression.Several studies on brain-damaged patients and normal subjects demonstrated the dominant role of the right hemisphere for prosody. In acute stroke settings, the assessment of dysprosody by bedside tests could help in localizing the lesion to the right hemisphere. Dysprosody, during epileptic seizures, has been linked to right hemisphere foci. The profile of anatomical correlation of prosodic syndromes (motor aprosodia for anterior and receptive dysprosody for posterior lesions) seems to parallel one of the aphasic syndromes of the left hemisphere.

Functional neuroimaging studies on normal subjects also provided a dichotomous scenario for linguistic functions such as the left hemisphere dominance for phonological and phonetic aspects versus the right hemisphere dominance for the emotional aspects.

Dysprosody might be amenable to behavioral treatments.

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A case of apraxic agraphia?

Apraxic agraphia is a very rare condition. The examiner should think about it when the patient shows normal linguistic capabilities (conversation is normal or almost normal) together with severely impaired writing. Apraxic agraphia is a peripheral writing disorder. Patients with apraxic agraphia have reduced ability to make the motor movements needed to write letters and sequence writting strokes. However, they usually have unimpaired capabilities of oral spelling. In the case of apraxic agraphia, writing is hesitant, imprecise and the disorder should not be explained by motor, sensory, extrapyramidal or cerebellar deficits and executive dysfunction (perseverations).
In case of stroke apraxic agraphia has been reported with frontal, parietal and thalamic lesions. Apraxic agraphia can manifest also with frontotemporal dementia and corticobasal syndrome.
Recently, I examined a 60 years old left-handed man, who had brain multiple ischemic stroke due to an hypercoagulability “trousseau’s syndrome”. The brain MRI showed 2 large lesions respectively of the left superficial territory of the posterior cerebral artery (occipital-temporal basal regions) and of the right parietal supramarginal gyrus.  Motor and sensory examination was normal.
This patient had normal linguistic output (normal conversation), mild denomination deficit, signs of visual apperceptive agnosia, alexia (letter-by-letter reading), and some features of apraxic agraphia. Oral spelling was spared. The patient’s writing was extremely low and hesitant as he did not remember how to do it.
An example of the patient’s writing on dictation is reported in the figure.
In this case, it is difficult to establish clinical-anatomical correlations (the same dysfunction is at the origin of both agraphia and alexia?), without further assessment but patients with atypical dominance could help in dissociating mechanisms of neurocognitive syndromes. Could you suggest your personal protocol to assess agraphia?

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Stimulate your cortex and eat less

BrainEating Eating disorders should raise up from dysfunction of neural processing in brain areas that are involved in emotional control, appetite regulation and body schema representations. In this context, eating disorders are located in the interface between the mind, body and the sense of self-agency.
It has been suggested that changes of the cognitive control exerted by the dorsolateral prefrontal cortex on the anterior ventral striatal pathway (a center predisposed to appetite regulation according to feelings of positive or negative reward) could trigger bulimic or anorexic behaviors.
One of the best evidence of such control cortical mechanisms on appetite regulation is the “Gourmand Syndrome” described by T. Landis and coll. Such a syndrome, which was identified in stroke patients with right hemisphere anterior lesions, consists of developing passion or manic thoughts for fine food and eating.
Even if the localizations and psychological mechanisms were globally known it would be still difficult to understand cortical changes in the brain in term of more specific circuits and neurotransmitters. To proceed to such a knowledge systematic studies with specific questionnaires or experimental cognitive eating paradigms (coupled with functional neuroimaging) should be conducted on patients with focal brain lesions or focal epilepsies.
Repetitive magnetic stimulation or transcranial direct current stimulation therapies, based on the result of those researches, would be tempted on patients (without brain lesions) and with eating disorders such as bulimia or anorexia or on patients with malnutrition or obesity

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Cervical Spondylotic Myelopathy (CSM): Nothing is easy!

CSM_1Although CSM is a frequent cause of myelopathy, its natural history is not clear, the clinical and radiological diagnosis might be particularly difficult and approaches to treatments are not standardized nor based on evidence medicine.
CSM is a degenerative condition of the cervical spine (spondylosis, disk herniation, spur formation, degenerative changes of facet joints, longitudinal ligaments and ligamentum flavum) leading to narrowing of the spinal canal (AP diameter < 13 mm), and to myelopathy and radiculopathy.
First symptoms are chronic suboccipital and cervical pain and decreased neck mobility but patients come generally to medical examination when they manifest weakness and paresthesia of arms and gait difficulties. In typical cases, the neurologist appreciates, together with reduced cervical motility, the presence of radicular signs of the superior limbs and corticospinal signs of the inferior limbs.
It should be never forgotten that false-positive and false-negative MRI results occur frequently in patients with radiculopathy and that therefore clinical findings about root involvement are fundamental when evaluating for surgery. Furthermore and not rarely patients have tandem spinal stenosis (simultaneous cervical and lumbar stenosis). Thus, complete neurological examination is determinant.
MRI examination is needed for diagnosis as the MRI images might show both spinal canal stenosis and signs of myelopathy. MRI diffusion tensor imaging (DTI) could be also useful.
However, in doubtful cases it is important to remember that, there is also the contribution of dynamic factors such as the effect of movements of the cervical spine on the spinal cord, and of vascular factors (spinal artery deformation and compression with resulting spine ischemia and hypoxia). Thus, it would be also important, for therapeutic decisions, to include, besides structural factors, the presence of cervical spine instability. Flexion-extension Rx views may detect cervical instability. Even when the diagnosis of CSM is done, but the disease is mild, it is not clear what it is the correct time for surgery as the deterioration rate remains unknown (deterioration is probably rare) and there are no radiological features able to predict the outcome (except probably for large and extended MRI T2 medullary hyperintensities). However, when radiological and clinical features are both significant but the patient is too invalidated by the condition, it would be probably too late for surgery. However, the main goal of surgery should be to avoid the progression of the disease and, therefore, there should be objective signs of myelopathy with clnical, MRI and evoked potentials tests.
Somatosensory and motor evoked potential could be useful to find signs of medullary involvement in doubtful cases.
Important elements to favor surgery are age < 75, the clinical severity and speed of progression of neurological symptoms and signs. Clinical severity is better evaluated with the aid of the modified Japanese Orthopedic Association (mJOA) scoring system. Surgical intervention is considered for score > 12 or >16. A favorable outcome (confirming that surgery was the best option) would be do demonstrate, after surgery, the improvement of evoked potential in comparison to the condition before surgery.
Surgical approach could be extremely varied depending of the site(s) of stenosis and associated degenerative lesions of disks and articulations. There would not be substantial differences of outcome between anterior and posterior approaches. Anterior approaches include: discectomy without or with bone graft, cervical instrumentation. Posterior approaches include decompressive laminectomy and foraminotomy, hemilaminectomy and laminoplasty.
Perioperative and delayed complications (among which, dysphagia, infections and other medical problems but also worsening of myelopathy) are not rare, especially in older patients. The use of combined anterior-posterior procedures show the higher risks of complications. Pre-surgery evaluation should include also neurologists and internal medicine specialists.
Probably most cases of mild or moderate CSM will not deteriorate or require surgery if the patient follow a strict conservative treatment consisting of cervical exercises with physical therapists, postural learning with occupational therapists, using collar in case of pain exacerbation, avoiding risky activities, avoiding cervical manipulations and prolonged flexion of the neck. However, for these patients, the neurological survey should be accurate and timed.

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Neurologic mysteries: Mild Encephalopathy with Reversible Splenium lesion (MERS)

MERSMERS is not a so rare clinical entity even if epidemiological data are scanty; the clinical presentation is variable such as the etiologies of this syndrome. However, although the splenium lesion is usually quite big, these patients do not show signs of posterior callosal disconnection (such as alien hand, left hand agraphia or apraxia, tactile aphasia or anomia, agraphia without alexia). They show some form of encephalopathy (delirium, confusion, transient consciousness alteration) and few cases have been reported with relatively pure psychotic features.
Causes include metabolic or toxic conditions such as epileptic drug withdrawal, epileptic status, hyponatremia and/or hypoglycemia, vitamin deficiency or malnutrition, hemolytic uremic syndrome, thyroiditis, neuroleptic malignant syndrome, EBV or influentia virus encephalitis, Kawasaki disease, Marchiafava-Bignami’s disease (in this condition demyelination usually occurs in the central part of the corpus callosum).
The brain MRI establishes the diagnosis showing the typically large isolated spherical lesion in the splenium of the corpus callosum. This lesion is usually hyperintense in T2, FLAIR and DWI images, with low ADC values and does not show contrast enhancement. In circumstances that are more exceptional other similar lesions could be present on the periventricular regions in the sémiovale center.
Although MRI feature of MERS are specific, some differential diagnosis should be thought, such as lymphoma, multiple sclerosis, and stroke.
EEG does not provide further elements to diagnosis and it is often normal. LCR examination would be indicated in most cases especially if the patient is still symtpomatic.
There are several hypotheses on pathogenesis: transient intramyelinic edema after generalized seizure, hyponatremia axonal damage, oxidative stress, AED toxicity and vasogenic mechanisms. Actually, the splenium of the callosum body probably receives blood from multiple arteries and the hypothesis of watershed mechanisms is less probable. The multitude of causes producing this unique lesion suggest a common but not specific pathogenic mechanism. This mechanism should have some similarity, I suppose, with the one at the origin of the subcortical occipital MRI abnormalities observed with posterior reversible encephalopathy.
Although some authors advanced the possibility of IgG or steroid pulse therapies, there is no specific therapy for MERS as the condition is usually fully reversible.

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Micrographia

MicrographiaMicrographia is a frequent symptom of Parkinson’s disease, often one of the first. Its association with the disease is straightforward: 75-90% of patients with Parkinson show micrographia, the presence of micrographia allows the diagnosis of PD in almost all cases. In other less frequent disorders, micrographia is associated with other parkinsonisms (Huntington’s disease, Wilson’s disease, Progressive Supranuclear Palsy, Binswanger’s disease and so on), which have degenerative, genetic or vascular causes and which all impair basal ganglia circuits as it happens with PD.
Micrographia denotes a small handwriting, which generally is also slow and less accurate. Micrographia can be also detected by asking to the patient to write by air movements of the fingers. Patients with handwriting do also small drawings (see the watch in the figure).
Specific software on computer and tablets allows measuring accurately the handwriting characteristics (size, duration, speed and fluency). Such digital measures of handwriting would help formulating the diagnosis of PD in the earlier phases. It would be important for PD diagnosis, even, without any specific measure, to compare visually the actual handwriting of the patients with the previous examples of the years before.
Two variants are described, although, they often coexist in the same patient. “Constant micrographia” is the constantly reduced form of the small handwriting. This is the general and distinctive feature of the micrographia itself. On the other hand, “Progressive micrographia” is the tendency for handwriting to reduce progressively its size more and more in the course of writing. This corresponds to the general “sequence effect”, a well-known phenomenon in patients with PD or other parkinsonisms, consisting in progressively reducing the amplitude and fluency of motor sequences (parkinsonian gait festination and/or gait freezing are examples). Similar to the progressive micrographia, in the case of gait festination, the patient involuntarily moves with short, accelerating steps, often on tiptoe, with the trunk flexed forward and the legs flexed stiffly at the hips and knees.
The “constant micrographia” is the direct expression of the dysfunction of dopaminergic motor circuits of the basal ganglia and can improve with levodopa or by training in handwriting rehabilitation. Progressive micrographia is determined by the dysfunction of larger connectivity of brain areas (including cerebellum or parietal and motor/premotor cortical areas) and less responsive to dopamine or rehabilitative programs.
Micrographia should be assessed and measured with digital instruments in PD patients, not only for diagnostic purposes but also to monitor and quantify the improvement of patients with pharmacological and rehabilitative treatments.

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Alzheimer’s disease: when the cure?

ALZHTo answer this question we should list some significant facts about the disease. There are 36 millions patients with the disease in the world, a diagnosis of Alzheimer disease is made every three seconds in the USA, the costs of the disease in the world are 600-800 billions of dollars and there is convergent evidence that indicates that the asymptomatic phase (before the onset of symptoms), last 15-20 years. Up to now, there is not a cure for the disease, although we know a lot on the genes and the proteins, which are involved.
The current available drugs (three acethylcholine-esterase inhibitors and one NMDA antagonist) show some efficacy only for 2/3 of patients and this effect lasts generally 6 months. Some studies regarding the effects of the association of these drugs are ongoing.
The CERE 110 is a phase I study that provided evidence that bilateral stereotactic administration of genetically engineered gene-therapy vector adeno-associated virus serotype 2 delivering NGF (AAV2-NGF)in to the nucleus basalis of Meynert is feasible, well-tolerated, and able to produce long-term, biologically active NGF expression. Phase II and III studies are needed.
EVP-6124 (Encenicline) is an α7 nicotinic acetylcholine receptor partial agonist under investigation for the symptomatic treatment of AD. Treatment with EVP-6124 in Phase I and II trials involving patients with mild-to-moderate AD was well tolerated and showed statistically significant improvements compared with placebo on cognitive and functional measures. Two Phase III studies under the title COGNITIV AD are ongoing.
Most phase III studies targeting Aß amyloid with monoclonal antibodies (Solanezumab, Crenezumab, Gantenerumab) did not show significant results. However, some positive trend n patients with mild or moderate disease was observed, data, which seems sufficient to extend these phase III trials to patients with the mildest form of the disease. Results will be available in few years.
The A4 trial will enroll normal individuals with amyloid accumulation, who are at increased risk for cognitive decline due to AD. 5000 clinically normal older individuals will be screened to identify those with increased amyloid accumulation on PET imaging; those individuals will be randomized into the anti-amyloid treatment arm with solanezumab or placebo arm. Individuals who do not show evidence of elevated amyloid accumulation may be eligible in an observation arm that will run parallel to the A4 treatment arm with identical cognitive assessments. A4 and LEARN study participants will be followed for 168 week treatment and observation periods.
The multicenter Dian-tu and API ADAD trials will enroll large samples of individuals who are carriers of different genetic variants of AD and will treat them with anti-amyloid monoclonal antibodies during the asymptomatic phase of the disease. The last two studies will give results after 2020.
Studies of drugs against secretases (MK/8931) are in phase II/III and results are expected on 2020.
Human studies on vaccines inducing immune response against Aß amyloid are still in phase I and II.
Therapies targeting tau proteins are for the moment only studied in animal models.
TTP488 is an orally active antagonist of RAGE (receptor for advanced glycation end-products). A phase II study did not provide significant results and showed concerns for safety of higher doses.
Pioglitazone, an insulin sensitizer of the thiazolidinedione class of peroxisome-proliferator activated receptor γ (PPAR-γ) agonists is under study on a phase III trial.
A Phase II study of saracatinib (AZD0530), a small molecule inhibitor with high potency for Src and Fyn, a family of kinases intervening in the synthesis of amiloid and tau, is ongoing.
In conclusion, there is nothing substantially new regarding a cure for the disease. Some optimism should be expressed for the future phase III studies including asymptomatic patients with the genetic variants of the disease and who will be trailed with monoclonal anti-amyloid antibodies. We have to wait still 5 years and probably even more for the results of such studies. However, it seems evident, from biological data we have, that Alzheimer disease is a multiple-mechanism disease requiring probably for a cure the combination of multiple drugs.

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Reduplicative Paramnesia

REDPARAThis syndrome is quite rare and there are no specific epidemiological data. It can be observed in both psychiatric and neurologic settings. In my personal neurologic career, I probably met thirty patients with this condition, most of them after frontal or temporal stroke on the right hemisphere. Few patients had Lewy body disease or other forms of dementia. Other few patients showed the disorder after traumatic brain injury (with hemorrhagic lesions or contusions predominant on the right hemisphere).
Patients with reduplicative paramnesia believe firmly that a familiar place (generally their own house), has been duplicated and exists simultaneously in two or more locations.
Most patients I met believed that the hospital was actually their own house disguised into the hospital. Others were convinced that the hospital was located in another town than the actual (for example Geneva instead than Lausanne). Other patients indicated a sort of chimeric assimilation: finally, a fusion between the hospital and their house took place. These false believes about places cannot be resolved by providing obvious and logical evidence of the contrary. The strength of this delusion (usually explained by the patient with improbable explanations, so called confabulations) is the key clinical element for the diagnosis of reduplicative paramnesia. However, differently than patients with schizophrenia, neurologic patients with reduplicative paramnesia appear collaborative or show little concern for their condition and do not feel themselves completely menaced by the delusion. The exact neural mechanisms of reduplicative paramnesia are not completely understood. The patients with brain lesions generally show memory difficulties together with visuospatial deficits and defective reality checking. Furthermore, this syndrome requires some distorted sensation of familiarity, which finally arises the patients’ doubts on the identity of places. Finally, there is some kind of anosognosia and/or a general reduction of awareness. There are no specific rehabilitation protocols for the treatment of this condition. Some empirical cues are systematically given to the patients to enhance reality orientation. Rarely patients need some pharmacological treatments for the delusion (low doses neuroleptics).
Actually, I follow, as outpatient, an 80 years old woman with a relatively pure form of reduplicative paramnesia 6 months after a medial temporal lobe stroke on the right hemisphere. Actually, she believes that the some furniture of her own house has been removed and is still in the hospital where she had rehabilitation. Her standardized neurobehavioral assessment showed moderate memory visuospatial and executive deficits and the patient verbalizes (despite with mild confusion) her doubts on what is real or not in her thoughts on the location of the furniture. Some suggestions for further assessment and/or treatment?

Posted in Cognition and Behavior, Stroke | 3 Comments

Recovery after stroke

RecoveryafterstrokeEarly prediction of functional outcome is important in stroke management to introduce rehabilitation programs with realistic objectives. These objectives should be periodically checked and continuously readapted with the salient clinical aspects of the patient recovery.
Outcome is generally better for deep cerebral hemorrhage than for subarachnoid hemorrhage and ischemic stroke. The influence of the lesion size and side is controversial, but the best predictor for a more negative outcome remains the severity of the deficits at the stroke onset. Most recovery of sensorimotor and cognitive deficits occurs in the first three months and this is undoubtedly the optimal time for intensive inpatient rehabilitation. Recovery continues at a slower pace throughout the first year or up to several years. Low-level functions (sensorimotor deficits processed by primary brain areas) often improve before than cognitive functions (attention, memory, language, and the other faculties processed by integrative or associative areas).
Age, sitting balance, severity of paresis, disability on admission, urinary incontinence, comorbidities, psychotropic drugs, previous stroke, interval before the onset of the rehabilitation treatment, and the adequacy of social support emerged as factors directly and indirectly influencing functional recovery
Cognitive deficits (particularly aphasia, neglect, and executive dysfunction, low Mini-Mental State Examination scores), and mood disturbances have a strong negative impact on the degree of autonomy after stroke.
In the earliest phases, recovery depends on the resolution of edema and reperfusion of the ischemic penumbra. During the following weeks, months and years, recovery is enhanced by the plasticity of the brain.
Mechanisms of brain plasticity are both structural (sprouting of fibers from the surviving neurons with formation of new synapses) and functional (extension of the cortical map, the emergency of alternative pattern of activation within the neural network including the damaged area, unmasking of previously existing but functionally inactive pathways, the use of alternative strategies and brain circuitries to resolve the same task).
All these mechanisms of recovery have been demonstrated in humans and animals and are modulated by experience and training.
Functional neuroimaging studies have provided considerable evidence that the reorganization of the injured brain can be modulated by activity, behavior, and skill acquisition. These studies suggest that combining therapies, foreseeing greater intensities of therapies, and increasing overall afferent inputs may improve stroke outcome.
While there is evidence that recovery of cognitive functions is supported by mechanisms of brain plasticity, the actual challenge is to identify which of the processes identified are important and how they can be enhanced by specific behavioral or pharmacological interventions.
Cognitive therapies for the individual patient should be supported by high quality evidence-based practice. Randomized controlled trials and rigorous meta-analysis studies are widely accepted as the more robust methodology for research into clinical treatments. Nevertheless, neurologic and cognitive rehabilitation is a particularly hostile field for application for this methodology because the great interindividual variability may be often, unfortunately, responsible for significant sampling errors. Unfortunately the available evidence which is low on the specificity of neurorehabilitative programs is at the origin of a great variability of treatments in different hospitals and clinics.
The best cognitive and physical neurorehabilitation programs are only defined by specialists who are able by themselves to perform detailed cognitive and neurologic assessment, who understand the complexity of the issues that are related to the neurologic recovery, and who know well the theoretical basis of neurology and neurorehabilitation..
In the field of neurorehabilitation I encountered some specialists with a very low scientific profile, insufficient clinical skills, limited knowledge of the rehabilitation literature, often proclaiming the good results of therapies which do not have any scientific or empiric evidence.
In this context I would like to quote Leonardo Da Vinci: “He who loves practice without theory is like the sailor who boards ship without a rudder and compass and never knows where he may cast.”

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The frontal lobe: the master and commander

MasterandcommThe frontal lobe is the main site of cognitive, emotional and behavioral processing. The prefrontal cortex, because of heavy bidirectional connections with all the other associative areas of the brain has long been assumed to have functions of control over other cognitive functions. This function has been termed
“executive”, meaning that rather than performing primary cognitive operations, such as memorizing, speaking and seeing, the frontal regions control the deployment of such capabilities, which are carried out elsewhere in the brain.
Therefore, the role of the frontal lobes is regarded as “supervisory” or “managerial” rather than being limited to the performance of any specific cognitive function. The frontal lobe is “the master and commander” of our brains. As per cognitive functions the frontal areas (as consistently demonstrated by fMRI studies) play a central role in working memory tasks. Working memory is the faculty that is responsible for the transient holding, associating and processing of new and already stored information, a fundamental process for reasoning, comprehension, learning and memory updating. Intelligent people or people gifted with the so called “fluid intelligence” generally have high capabilities of working memory.
As per the cognitive deficits patients with frontal lobe lesions show working memory deficits, poor logic and judgment, diminished sustained attention and mental speed, poor capacities of planning and organizing, poor abstraction, mental inflexibility, difficulties to control automatisms and task-switching,
The frontal lobes are the “master and commander” of emotional and behavioral processing too.
Evidence of the role of the prefrontal cortex in behavior and personality changes comes from the description of patients with frontal lobe damage. Such patients tend to be emotionally impulsive and poorly affectively regulated. Their behaviors include decreased concern with social propriety, environmental dependency, utilization, imitation and stereotyped behaviors, restlessness, exuberance, euphoria, facetiousness, extroversion, lack of restraint, purposelessness, childish behavior, distractibility, egocentricity, grandiosity, capriciousness and instability, social and sexual disinhibition, poor judgement, diminished foresight, social withdrawal, absence of tact, concreteness, acting on simple motivations, impulsiveness, self-centeredness, immorality, inertia, lack of ambition, indifference to the environment, satisfaction with inferior performance, slowness in thinking, bradypsychism, lack of emotional expression, decreased self-concern, shallow affect, depressed outwardly directed behavior and social sense, indifference, and alexithymia, lack of empathy and impaired theory of the mind (the ability to attribute mental states to others and to oneself), ritualistic or compulsive behaviors. Furthermore, several of these conditions may often occur together in the same patient.
Damasio and Stuss suggested that all behavioral and emotional changes due to frontal system damage might be a personality disorder where lack of control and self-reflectiveness (vulnerability to interference, impoverished judgment, and inability to self-correct and self-monitor) are the key features.
Hence, the DSM taxonomy of personality disorders (paranoid, schizotypic, antisocial, borderline, histrionic, narcissistic, avoidant, and obsessive–compulsive) seems to fit well with the so-called “frontal” behaviors.
The rehabilitation of the individual with a dysexecutive/frontal syndrome is a true challenge for the clinician and requires complex multidisciplinary approaches.

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FALSE MEMORIES

DRMThe Deese–Roediger–McDermott (DRM) paradigm (Roediger and McDermott, 1995) is a procedure to study false memories. In this paradigm, individuals are induced to falsely recall/recognize a nonstudied word (e.g. sleep), which is defined as the “critical lure”, through the previous study of a list of related words (e.g. bed, rest, awake, tired, dream, etc.).
Another example: individuals are presented with these words: door, glass, pane, shade, ledge, sill, house, open, curtain, frame, view, breeze, sash, screen, and shutter. These words that are strongly associated with the word window (the critical lure). When these individuals will try to recognize previously presented words (such as door, curtain, house, open etc…) in lists which contain also nonstudied words (as window) they will falsely recognize “window” as a studied word.
This ‘memory illusion’ effect has largely proved to be a robust phenomenon whereby the false recall/recognition rate can be as high as the true recall/recognition rate. Furthermore, such false memories are incredibly associated with high levels of confidence.
One hypothesis to explain how false memories occur in the DRM paradigm is that, when we hear list items during encoding or retrieval, we think about the critical non-presented associated word (the critical lure) because memory processes (once again in both phases of encoding or retrieval) spread through semantic (or categorical) associations. This could be at origin of some “familiarity feeling” with the word corresponding to the critical lure. The recognition of the nonstudied word (the critical lure) in successive words presentations could be the consequences of this sense of familiarity. Actually the degree of semantic association or strength between the studied words and the critical lure is critical for successive false recognitions.
To overcome this natural and almost unconscious occurrence of such false memories (critical luries) we should use some powerful capacities of inner control and monitoring. Thus, these capacities could be enhanced when the initial encoding of the studied words is potentiated (for example associating verbal and visual stimuli, or pronouncing the word aloud) or when the subjects are warned that they could falsely recognize items basing on spontaneous associations.
However, the DRM paradigm shows us how our recollection of memories could be easily influenced.
Indeed it has been shown, as it was naturally supposed to be, that fatigue, sleep, emotions, age, gender, and mood states (anxiety or depression) influence the individual’s performances with the DRM paradigm.
It is not completely clear whether and in which state of Alzheimer’s disease, patients perform with the DRM paradigm differently than normal subjects (matched for age and cultural level). The DRM paradigm has been also used to study amnesic patients with different pathologies, other form of dementia and schizophrenia.
Unfortunately lists of words are quite variable across the experiments, and different studies can give different results within the same categories of patient.
I always thought that is would be interesting to find persons who are able to overcome the natural tendency to produce false memories with the DRM paradigm. High power of control on false memories could it be one of the prerequisites of genius?

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Brain imaging and bioimaging for Parkinson’s Disease

Pathologisch (2)Normal (2)Bioimaging for Parkinson’s Disease (PD) could be useful, especially for those patients consulting for the first time and not fulfilling entirely the diagnostic criteria. I refer to patients with limited features of the disease (atypical tremor, predominant postural tremor, incertitude as the progression, missing or unclear data about the response to levodopa), patients with unusual features (lower-body predominant parkinsonism, falls, cognitive deficits, dysarthria or urinary symptoms at the beginning of the disease, inferior limb tremor, strictly unilateral disease, lack of asymmetry), or to patients with additional white matter hyperintensities or vascular lesions on the brain MRI. Even if the routine use of neuroimaging is not recommended in all patients with PD, for the first clinical evaluation, I almost always demand a brain MRI examination to a radiologist who is specialized in neuroradiology. Actually, for the first evaluation, there is almost always the patient’s request to confirm the clinical diagnosis with some additional data. Brain MRI could be useful to exclude subcortical or infratentorial tumors or malformations and, furthermore, to assess for white matter lesions (which could be responsible of some symptoms that will not respond to levodopa as dysarthria or lower-body predominant parkinsonism). Finally, MRI examination allows to detect, apart from vascular lesion, the presence of signs that are specific to parkinsonian disorder other than PD. These are the ‘hot-cross-bun” sign and the reduced MRI T2 signals of putamen in multiple system atrophy, and midbrain, superior and cerebellar peduncle atrophy in progressive supranuclear palsy. Brain MRI is necessary for younger patients to look for iron or calcium deposition in basal ganglia structures. Functional imaging of the dopamine transporter using SPECT and (123I) ioflupane (DaTscan) is a very useful tool to differentiate PD from essential tremor. The specificity of the DaTscan for PD is very high (93-97%). DaTscan is also normal in other mimics of PD such as drug-induced parkinsonism, psychogenic tremor, central nervous system infections or other autoimmune disorders, hydrocephalus, pallidal atrophies, X-linked dystonia– parkinsonism and dopa-responsive dystonia. However, it should be absolutely noted that the DaTscan results could be confounding in differentiating PD from other parkinsonian disorders (about 10% of cases), especially in the early phases of the diseases, when the clinical picture is incomplete. This could be case of the supranuclear progressive palsy or Lewy body disease or others. I always ask for a DaT-Scan in young patients with early onset PD. Actually, I should say that, against official recommendations of the neurologic associations, my “clinical threshold” for demanding a DaT-Scan is finally low. Often, also when the clinical picture could be sufficiently clear and diagnostic criteria are fulfilled, several patients, at the first evaluation, even when the brain MRI is normal, seem to request some instrumental or laboratory confirmation of the disease before starting a pharmacological treatment. This is the case when a so-called “political” Dat-Scan is performed. 123iodine-meta-iodobenzyl guanidine (123I-MIBG) myocardial scintigraphy, showing postganglnionic sympathetic cardiac denervation in PD could also distinguish PD from other causes of parkinsonism. Some other techniques are are in development. These techniques are the 7T-MRI scanning and transcranial sonography, examinations which detect directly the abnormalities of the substantia nigra. Do you use  “political” DaTscans?

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rTMS for chronic migraine?

20150421_094522_1Chronic migraine is a disabling condition defined as more than 15 headache day by month for more than 3 months, of which more than eight episodes are migraineous. The diagnosis of this disorder requires the assumption that a medication overuse headache has been excluded. However, the role of overuse medication for chronic migraine is practically impossible to ascertain as the majority of patients with chronic migraine inevitably consume high quantities of drugs for pain (as the life-egg-chicken problem). Prevalence rates of chronic migraine could be 1-5% in the general population. Furthermore, 2-5% of patients with episodic migraine (less than 15 headache days by month) could evolve to chronic migraine. Chronic migraine is a disabling condition as it causes loss of time from working and social activities. At work, these patients are less efficient and productive. Depression and anxiety are inevitably (80-100% of patients). Prophylactic drugs that are used for episodic migraine are often not efficacious for chronic migraine or have side effects. BOTOX intramuscular injection on several points the face, head and neck are the only approved pharmacological treatment for this disorder but more than 3 cycles of treatment could be necessary to obtain some results. The neurologist should also take in account to treat co-morbidities and other trigger factors (for example social factors) that are often present in patients suffering of chronic migraine
Finally, repetitive magnetic stimulation (rTMS), could be a useful neuromodulating treatment for chronic migraine when all the other treatment failed. rTMS (on the occipital visual cortex) showed already encouraging results for episodic migraine prevention and for the treatment of the migraneous aura.
rTMS is a noninvasive method used to stimulate small regions of the brain. During a rTMS procedure, a magnetic field generator, or “coil” is placed near the head of the person receiving the treatment (see the machine in my office in the picture). The coil produces small electrical currents in the region of the brain just under the coil via electromagnetic induction. The coil is connected to a pulse generator, or stimulator, that delivers electrical current to the coil. The magnetic field applies to the brain up to 3-7 cm under the skull, about 2000 times during a standard session (15-30 minutes). Thus, rTMS can induce increases or decreases in excitability of large populations in deep areas of the brain. Excitation or inhibition of thalamo-cortical circuits could reset pain neural pathways.
The treatment has almost no side effects. However, patients with epilepsy are excluded from the procedure because of the risk of crisis. Rarely the procedure could give mild local discomfort and pain. Some patients experience transitory changes in working memory and mood.
However, results of recent studies of rTMS are still preliminary and sometime negative for chronic migraine. Such studies indicate also a powerful placebo response to the sham stimulation (probably due to the suggestion to become  magnetized! (“I magnetize you the doctor said”). It is not yet clear which the part of the brain to stimulate is and this could be a very important limiting factor for the procedure.
In the future, neuromodulation with rTMS will probably have a better place in chronic migraine treatment, especially because of its attractive safety profile. However, now, which protocol would you suggest for rTMS in patients with chronic migraine?

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Pusher syndrome

pusherPatients with the pusher syndrome are characterized to push toward the weak side of the body, generally the left side (on a coronal plane) after a right hemisphere lesion. This behavior puts them at high risk of falling. These patients resist to the examiner’s attempts of rectifying the correct orientation by pushing the body with the unaffected limbs toward the affected ones, generally on the left. A rarer « posterior » variant has been reported in which patients push posteriorly on a sagittal line.
The pusher syndrome occurs in patients with acute right hemisphere stroke. It is less frequent with other brain diseases (tumors, multiple sclerosis).
Rehabilitation of such patients could be challenging as the pusher syndrome appears the effect of a reflex behavior and the patients seem resistant to learn compensatory strategies. Patients with the pusher syndrome have longer times of rehabilitation in comparison to other stroke patients.
Several scales are adopted in clinical studies to establish a diagnosis of the condition and to grade its severity (the Pusher index, the Melbourne Index Scale, the Scale for Contraversive Pushing, the Lateropulsion Scale). However, on a clinical perspective, the condition of the Pusher syndrome should be considered just when the patient is observed pushing constantly on one side, no matter in what position he is (standing, sitting or lying). The patient with the pusher syndrome pushes almost always toward the left side of the body and the syndrome is almost always associated, at least as I observed in my profession, with signs of left spatial unilaterl neglect (the condition of ignoring the left side of the body in several sensory modalities).
The brain areas that can be damaged in patients with the Pusher Syndrome overlap with those that are associated with spatial neglect. Probably for the pusher syndrome, the damage of parietal thalamo-cortical connections is most relevant.
The ultimate mechanism of the pusher syndrome could be an incorrect perception of the verticality of the body because of two combined conditions: a loss of sensory stimuli from the affected side and the presence of left spatial neglect. In this perspective, the pusher syndrome has been called also « graviceptive neglect ».
Our perception of the gravity line of the body is constructed on the base of visual (the visual surrounding) and sensory stimuli (proprioceptive, haptic and vestibular body inputs) and it can be studied in a dark room by dissociating and manipulating experimentally the different stimuli. The pusher syndrome should be studied in the Space in the absence of gravity.
Rehabilitation programs should assess and recenter the body gravity line by adapting the patient’s movements and posture to all the sensory modalities, although there is, as usual, some controversy as per the sensory modality to prefer.

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Room-tilt illusion

Room-tiltThis illusion is quite rare and I can remember on my fingers the patients with it whom I met, generally in emergency settings. For the majority of them the illusion was transitory lasting generally minutes and was accompanied by other neurological symptoms and deficits (vestibular and not).
The room-tilt illusion consists of a clear and bright visual view of an upside down tilt (180 degree on a coronal plane) of the surroundings. Even if in an upside down way, the walls and the objects of the room are perfectly perceived, without probably no distortion (or some sort of rotation). The patients are usually frightened about that illusion and think to have stoke.
This illusion is generally considered the results of a lesion or dysfunction in the brainstem circuitries that connect the vestibular-otholitic system (the inner ear organ of equilibrium) to the higher brain associative visual areas (parieto-temporal regions and posterior insula). According to this last assumption, the room-tilt illusion is a syndrome of the higher central vestibular functions. However the exact neural mechanism of the room-tilt illusion is not yet known.
Finally for the majority of these patients (as the ones I met in my profession) the responsible lesion is ischemic (AIT or stroke) and located in the lower brainstem areas. However, the syndrome is known to occur less frequently with pure vestibular disorders (such as Meniere disease, bilateral vestibular affections or benign positional paroxysmal vertigo), and also as a partial epileptic crisis (vestibular epilepsy) in patients with cortical lesions.
I found the illusion also in a patient with multiple sclerosis whose neurological deficits worsened after a urinary infection, and in a patient with migraine who was hyperventilating during the migraine crisis. In the scientific literature, the illusion has been described also in isolated patients with Parkinson’s disease, cervical myelopathy, polyradiculoneuritis and cerebellar diseases (ischemic or degenerative).
Finally patients with the room-tilt illusion have an upside-down misperception of verticality. In normal conditions the dimension of verticality is assured by an accurate interaction between the vestibular system (together with other sensory afferent inputs) and the visual system. The results of such neural processing is adapted to 3-D coordinates of the self and of the visual scene. When there is a mismatch between vestibular peripheral inputs (altered by the lesion) and the other sensory systems, the higher cortical centers (visual associative areas) must re-calibrate these abnormal signals and could do it with the result of a complete scene inversion on the coronal roll plane.
The room-tilt illusion is a rare symptom, and generally it is transitory. Therefore, it would be quite difficult to study it with experimental paradigms, such as for example (the first one that came to my mind) measuring the speed and quality of reading of inverted and not inverted degraded words. We know that rotation of a furnished room in controlled conditions can reproduce the illusion only partially in normal subjects.
We are so accustomed to see the visual world as it is that we are not aware at all of the complexity of the information that the brain process (in multiple regions) in order to let things appear at the right places. When the brain is damaged in his visual association areas the visual world changes, then we realize how much fragile is the consciousness and the awareness of the self. Things probably do not exist as they appear when they are not processed correctly by a visual brain.

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When 22-7 is more difficult than 99-12

DysscalculiaFor arithmetic facts (i.e., table facts, such as 2 x 3 = 6), there is strong evidence that cerebral damage can cause selective impairments within basic arithmetic operations. However, to understand the brain underpinnings of arithmetic abilities, it is necessary to distinguish the process of retrieval of arithmetic facts from calculation procedures. Actually, several neuropsychological reports described isolated deficits within calculation procedures and some studies documented a double dissociation between performance in arithmetic facts retrieval and calculation procedures, even within the same operation. However, brain functional systems subsiding calculation procedures are still poorly characterized in comparison to functional systems of basic arithmetic facts.
Dehaene and Cohen offered some explanations how calculation processes map onto brain anatomy (the “triple code” hypothesis). Regarding arithmetic procedures, the authors suggested that working memory, processed by dorsolateral prefrontal cortical-subcortical systems, is an essential component for problems that require the temporary storage of intermediate results, for instance during ”carrying over” or borrowing operations. A visuo-spatial store, supported by the same brain regions, is complementary functioning to keep on-line spatial layouts and digits of ongoing multi-digit calculation. Both phonological and visual working memory systems are part of a large network of areas in the left (for the verbal working memory) and in the right hemisphere (for the visuo-spatial working memory system) that includes temporal-parietal and frontal-subcortical regions.
This view is different from the one proposed by McCloskey and colleagues that conceives the existence of three serial modules for calculation: input number processing, calculation procedures and output number processing. Within the module of calculation procedures, neural processes, whcih are specific and selective for each operation and independent from the retrieval of arithmetic facts, are presumed to exist. Based on a cognitive neuropsychological framework, McCloskey et al. distinguish between disorders of number processing (reading, writing, producing, comprehending, or repeating numbers) and disorders of calculation (arithmetic facts, knowledge of procedures). Recent studies also suggest that number representation, arithmetic fact knowledge and procedural aspects of calculation should be studied with a specific within-task approach more than a between task approach and that individual differences in competences, training and in strategy use (procedural vs retrieval) can strongly influence arithmetic problem solving.
Me and other authors published (Neurocase 2013;19(1):54-66) a case of a 69-year-old professor of mathematics, examined two years after a subcortical hemorrhagic stroke, who presented with a persistent form of dyscalculia exclusively limited to the procedure of subtractions with borrowing (i.e. great difficulties for operations as 22-7 when operations as 99-12 were easy to perform). Patient’s errors in subtractions with borrowing mostly relied on his automatic and inadequate attempts to invert subtractions into the corresponding additions (e.g. he used  to transform 22-7=x into 7+x=22). The hypothesis is that difficulties with the inhibitory components of executive and working memory tasks (he had problems with the Stroop test and go-nogo tasks) could be responsible of this specific impairment for subtractions with borrowing.
Clinical and experimental findings of this single-case study are compatible with both the Dehaene and Cohen’s model (as per the role of working memory and executive functions in calculation procedures) and the McCloskey’s model (assuming that brain lesions can involve selectively neural pathways for different calculation procedures). We further speculated, based on MRI findings of that case, that a deficit in subtractions with borrowing could be related to left-hemispheric subcortical damage involving thalamo-cortical connections.
Do you assess calculation routinely in cognitive impaired patients? How do you do that?

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Nerve Agents

Nerve AgentsAlthough biological and chemical warfare are the aberration of medical sciences they will be always a subject of military studies as war is an unavoidable condition of the human nature itself.
Although we should always avoid excessive alarmism, the neurologist should be prepared to public health emergencies that are the consequences of neurotoxic weapons. The use of nerve agents in recent conflicts (Iran-Iraq war [1984-1987], Goutha, Damascus [2013]) and bioterrotistic actions (Tokio sarin attacks in 1994 and 1995) validate this assumption. Nerve agents (e.g Sarin, Tabun. VX) are able to cause human death in seconds at very low concentrations. Less than 1 mg of most of these agents can kill a man.
Nerve agents cause an irreversible inhibition of the acetylcholinesterase enzyme (AChE), which, in its turn, enhances massive stimulation of the cholinergic muscarinic and nicotinic receptors, and leads to a life-threatening cholinergic crisis. The vapors enter first in contact with the eyes, resulting in myosis and painful loss of accommodation and dark adaptation. Other early symptoms are conjunctival injection lacrimation, rhinorrhea, salivation, diaphoresis, chest tightness, bronchorrhea and bronchial reactivity with wheezing, and respiratory distress (similarly to an acute asthmatic attack). Bronchorrhea could be so profuse to mime pulmonary edema.
Nerve agents cross easily the alveolar-capillary barrier and systemic cholinergic symptoms manifest promptly (sweating, abdominal cramps, pain, nausea, vomiting, tenesmus, diarrhea, increased bowel movements and urinary incontinence). The cholinergic transmission of the heart and brain (which is particularly rich of acetylcholine receptors) is rapidly affected. The victims manifest bradycardia or tachycardia, hypotension/hypertension and signs of encephalopathy, such as headache, vertigo, dizziness, agitation, confusion, hallucinations, loss of consciousness, seizures and failure of the central respiratory drive with central apnea. Brain dysfunction is mediated by both the altered cholinergic transmission and hypoxia due to respiratory failure. Cholinergic overload on nicotinic receptors induces numbness, fasciculations and muscle twitching (even to a degree that mime convulsions) of the limbs. Tremor has probably a central origin. Successive ATP depletion and probably myonecrosis cause a diffuse flaccid paralysis, which includes the diaphragm muscle.
In war attacks, peripheral and systemic symptoms of nerve agent vapors could manifest almost simultaneously and death can occur in minutes. As these vapors are odorless and colorless, the victims, at the beginning do not fully understand the events, but they notice that other people around are severely ill or near death. Death is generally due to respiratory failure and suffocation. The narratives of survivors, seeing asphyxiating or seizing people around, are chilling.

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Parkinson disease and anxiety

PD and anxietyI think that anxiety is one of the most common non-motor symptom of Parkinson disease (PD) at the early stages of the disease. An anxiety profile that is specific to PD has not been defined. DSM diagnostic criteria of anxiety does not apply specifically to PD. Furthermore, the characteristics of PD related anxiety have not been so extensively investigated. I think that Impulsivity might be particularly frequent for patients with PD and anxiety. Anxiety could also dissociate from depression in PD patients. The Parkinson Anxiety Scale could be useful, as it has been specifically constructed for PD patients.
What I find noteworthy is that patients with PD might appear at the first sight apathetic even when worries and anxiety are well present. That is a known phenomenon, as PD patients show reduced spontaneous facial or body movements (bradymimia, bradikinesia). Thus, doctors and caregivers should challenge the appearances and should actively ask for anxiety symptoms.
Anxiety affects 40% of patients with Parkinson and anxiety is probably the behavioral change that has the greatest impact on the patients’ quality of life. However, it is highly probable that anxiety is underestimated in PD patients and that it is often untreated.
In PD, anxiety is not simply the consequence of copying with the motor disability (even if psychological issues are important), as it is admitted that neurotransmitter changes due to the disease itself occur in those brain networks (frontal-subcortical and extended limbic lobe circuitries) which are involved in emotional and mood regulation. For PD patients (as well as for patients with Alzheimer disease) anxiety (together with depression) might precede of several years the motor symptoms of PD.
On the middle and late stages of PD, when motor fluctuations (dyskinesia and OFF-periods) are important, patients experience a great anxiety in the OFF-periods. On clinical grounds, it is well known that worry is much more important in OFF phases than with dyskinesia. On the other side, it is well recognized that anxiety (and depression) can themselves worsen motor symptoms and fluctuations. The treatment of the anxiety symptoms could be more difficult when cognitive deficits and motor fluctuations are both present. Anxiety could be a behavioral equivalent of the frontal syndrome in case of cognitive impairment.
Anticholinergic drugs (to treat anxiety) might have important side effects for frail elderly PD patients. The effect of deep brain stimulation remains uncertain for the symptoms of anxiety. Dopa-agonists and SSRI together with cognitive behavioral therapies and counselling can improve symptoms of anxiety. However, dopaminergic drugs could also aggravate the symptoms of anxiety and induce psychosis. Psychosocial interventions could be helpful. It would be interesting to study more extensively the effects of relaxation techniques, yoga and massages on PD related anxiety.
There is an urgent need for systematic studies in the pharmacological and non-pharmacological management of anxiety in PD. Anxiety occurring with Parkinson disease is a neuropsychiatric disorder.

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“Nummular headache”: a 5 CHF coin-shaped headache

Nummular headacheNummular headache is the term given to a condition characterized by a continuous or intermittent pain that is felt in a contoured and fixed coin-shaped elliptic area (2-6 cm, usually as a 5 CHF coin) of the scalp, generally on the parietal area. Rarely the disorder could be bifocal or multifocal. Nummular headache is a form of epicranias (group of headaches and neuralgias stemming from epicranial tissues).
The pain is generally moderate but patients can present strong exacerbations or disturbing tingling sensations or also allodynia and hyperpathy by touching or combing the hairs in that region. Rarely patients report this pain after muscular exercise, after Valsalva maneuvers or during menses. Some patients have some association of nummular headache and migraine (however, in these cases the evolution of the two conditions appear quite independent). Patients can rarely present some local scalp changes (for example alopecia). Patients generally fear to have some cerebral disorder and seek consistently for medical advice. Brain MRI or CT-scan are usually demanded to exclude secondary causes and to reassure the patients on the absence of brain anomalies. The reproduction of the patient’s pain by moderate pressure over that coin-shaped region or by stretching the scalp of that area (usually I do with the knuckles of my hand) indicate the local origin of the pain. This area is usually well delimited, and this is an important feature to retain the diagnosis of nummular headache. In the majority of cases, it is not possible to determine any specific cause to the disorder. The pain, for its characteristics, should originate from little nerve branches there.
In exceptional circumstances, patients with nummular headache are diagnosed with meningiomas, arachnoid cysts, craniosynostosis, calcific hematomas of the scalp or other vascular anomalies (aneurysms or other) of the superficial arteries of the scalp. For this reason, during the clinical examination, the examiner should check for vascular abnormal pulsations or bruits over the scalp. In that cases scalp ultrasonography could be a useful investigation. Some patients develop nummular headache after transphenoidal or other meningeal surgery, which could suggest a meningeal or central sensitization mechanism for pain. A central or peripheral trigeminal sensory mechanism is also suggested by the fact that patients with pituitary adenomas might have pain referred to the vertex of the skull. Other authors suggested that the disorder is due to a local diminished threshold for pain even if for unknown reasons. Few patients with nummular headache were found with autoimmune disorders.
Schwartz et al. made a review of 256 cases reported in the scientific literature (http://www.ncbi.nlm.nih.gov/pubmed/23616207).
Treatment with Gabapentin could be helpful but generally is not curative. Other patients responded to amytriptiline, carbamazepine, indometacine or other NSAIDs or even to TENS application. Some patients improve with Botox scalp injections. I propose to try ice bags or cool spray. There are few data on patients who underwent scalp focal resections to treat the disorder.
The scientific literature give few data on the long-term follow-up of this disorder. I think that most patients can have temporary or long term remissions which could be independent from any therapeutic interventions.
Even if I diagnosed this condition for few patients, by examining the literature data, as also indicated by Pareia et al (http://www.ncbi.nlm.nih.gov/pubmed/19810895), I have the feeling that, once that a normal brain MRI excluded other possible primary disorders, in most of these patients, the treatment is seldom necessary and simple reassurance is sufficient.
I think that nummular headache is still a mysterious disorder.

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