A clinical and neurophysiological motor signature of Unverricht-Lundborg disease.

OBJECTIVES: Unverricht-Lundborg disease (ULD) is the most common form of progressive myoclonus epilepsy. Cerebellar dysfunction may appear over time, contributing along with myoclonus to motor disability. The purpose of the present work was to clarify the motor and neurophysiological characteristics of ULD patients. METHODS: Nine patients with genetically proven ULD were evaluated clinically (medical history collected from patient charts, the Scale for the Assessment and Rating of Ataxia and Unified Myoclonus Rating Scale). Neurophysiological investigations included EEG, surface polymyography, long-loop C-reflexes, somatosensory evoked potentials, EEG jerk-locked back-averaging (JLBA) and oculomotor recordings. All patients underwent brain MRI. Non-parametric Mann-Whitney tests were used to compare ULD patients' oculomotor parameters with those of a matched group of healthy volunteers (HV). RESULTS: Myoclonus was activated by action but was virtually absent at rest and poorly induced by stimuli. Positive myoclonus was multifocal, often rhythmic and of brief duration, with top-down pyramidal temporospatial propagation. Cortical neurophysiology revealed a transient wave preceding myoclonus on EEG JLBA (n=8), enlarged somatosensory evoked potentials (n=7) and positive long-loop C-reflexes at rest (n=5). Compared with HV, ULD patients demonstrated decreased saccadic gain, increased gain dispersion and a higher frequency of hypermetric saccades associated with decreased peak velocity. CONCLUSION: A homogeneous motor pattern was delineated that may represent a ULD clinical and neurophysiological signature. Clinical and neurophysiological findings confirmed the pure cortical origin of the permanent myoclonus. Also, oculomotor findings shed new light on ULD pathophysiology by evidencing combined midbrain and cerebellar dysfunction.

Posterior reversible encephalopathy syndrome (PRES) and hypomagnesemia: A frequent association?

Posterior reversible encephalopathy syndrome (PRES) is a serious neurological condition encountered in various medical fields. Pathophysiological factor(s) common to PRES cases of apparently unrelated etiologies are yet to be found. Based on the hypothesis that hypomagnesemia might participate in the cascade leading to PRES, our study sought to verify whether hypomagnesemia is frequently associated with PRES regardless of etiology. From a retrospective study of a cohort of 57 patients presenting with PRES of different etiologies, presented here are the findings of 19 patients with available serum magnesium levels (SMLs) during PRES. In the acute phase of PRES, hypomagnesemia was present in all 19 patients in spite of differences in etiology (including immunosuppressive drugs, hypertensive encephalopathy, eclampsia, systemic lupus erythematosus, iatrogenic etiology and unknown). SMLs were within normal ranges prior to PRES and below normal ranges during the first 48h of PRES, with a significant decrease in SMLs during the acute phase. In this retrospective study, constant hypomagnesemia was observed during the acute phase of PRES regardless of its etiology. These results now require larger studies to assess the particular importance of acute hypomagnesemia in PRES and especially the possible need to treat PRES with magnesium sulfate.

[Severe dysautonomia revealing Wernicke's encephalopathy]. / Dysautonomie sévère révélatrice d'une encéphalopathie de Gayet-Wernicke.

INTRODUCTION: Wernicke's encephalopathy, a pathology caused by vitamin B1 (thiamin) deficiency, is often difficult to diagnose and can lead to severe cognitive sequels if left untreated. CASE REPORT: We report the case of a 42-year-old HIV-positive women who, four days after recurrent episodes of vomiting, developed severe dysautonomia and symptoms suggestive of Wernicke's encephalopathy. Treatment with parenteral thiamine induced dramatic improvement within a few days. CONCLUSION: This case report highlights an unusual presentation of symptomatic thiamin deficiency associating severe dysautonomia with the classical manifestations of Wernicke's encephalopathy. As dysautonomia is frequently the earliest sign of beriberi, this case illustrates the continuum between these two diseases whose cause, symptomatic thiamin deficiency, is the same. It also draws attention to the multiple risk factors that may be associated, leading to symptomatic thiamin deficiency. This deficiency, while often overlooked, is frequent in HIV-infected patients. Finally, this case contributes to the discussion on the possible genetic polymorphism that may make a limited deficiency symptomatic.

[Wolfram's syndrome presenting as a cerebellar ataxia]. / Ataxie cérébelleuse révélant un syndrome de Wolfram.

INTRODUCTION: Wolfram syndrome is a genetic disease with recessive autosomic transmission, associating early-onset diabetes mellitus and bilateral optical atrophy. CASE REPORT: We report the case of a 47-year-old patient for whom we diagnosed a Wolfram syndrome in view of a late neurological syndrome in association with ataxia and bilateral horizontal nystagmus. The brain resonance magnetic imaging revealed a major atrophy of the brainstem and cerebellum. CONCLUSION: Wolfram syndrome is a rare pathology, with fatal consequences before the age of 50. The association of diabetes mellitus and optical atrophy, especially when there are other symptoms (ataxia, deafness, diabetes insipidus, neuropsychiatric manifestations or urinary tract disorders) should lead to this diagnosis and to carry out a genetic confirmation.

[Multiple sclerosis: immunomodulators, education, and self-injection]. / Sclérose en plaques: immunomodulateurs, éducation et auto-injection.

One hundred and sixty four patients of the Poitou-Charentes area suffering from multiple sclerosis (MS) and treated with an immunomodulating agent for more than 3 months completed a self-administered questionnaire. More than 60p.cent of the patients performed self-injection. For both modes of injection studied (subcutaneous or intramuscular), self-injection was significantly more frequent among patients who were received training and followed via telephone assistance conducted by a nurse with specialized training in MS. Our study demonstrated that waste disposal (needles), especially among patients performing self-injections, remains an important problem. Efforts must be taken concerning this important healthcare issue.

Neurosurgery in Parkinson's disease: the doctor is happy, the patient less so?

Despite the overall excellent outcome of neurosurgery in patients with Parkinson's disease, there is often a contrast between the improvement in motor disability and the difficulties of patients to reintegrate a normal life. In this study, the personal, familial and professional difficulties experienced by patients two years after bilateral high frequency stimulation of the subthalamic nucleus were carefully analyzed. To avoid such socio-familial maladjustment, we strongly suggest taking into consideration the patients' psychological and social context before the operation and during the post-operative follow-up.

Neurosurgery in Parkinson disease: a distressed mind in a repaired body?

OBJECTIVE: To prospectively evaluate the impact of subthalamic nucleus (STN) stimulation on social adjustment in patients with Parkinson disease (PD). METHODS: Before and 18 to 24 months after bilateral STN stimulation, the authors assessed 29 patients with PD for motor disability, cognition (Mattis dementia rating scale, frontal score), psychiatric morbidity (Mini-5.0.0, MADRS, BAS), quality of life (PDQ-39), social adjustment (Social Adjustment Scale), and psychological status using unstructured in-depth interviews. RESULTS: Despite marked improvement in parkinsonian motor disability, the absence of significant changes in cognitive status, and improvement of activities of daily living and quality of life by the end of the study, social adjustment did not improve. Several kinds of problems with social adjustment were observed, affecting the patients' perception of themselves and their body, marital situation, and professional life. Marital conflicts occurred in 17/24 couples. Only 9 out of 16 patients who had a professional activity before the operation went back to work after surgery. CONCLUSION: After STN stimulation, patients experienced difficulties in their relations with themselves, their spouses, their families, and their socio-professional environment. The authors suggest a multidisciplinary psychosocial preparation and follow-up to help patients and their entourage cope with the sudden changes in their existence following successful neurosurgery.

Clinical and economic results of bilateral subthalamic nucleus stimulation in Parkinson's disease.

BACKGROUND: High frequency stimulation of the subthalamic nucleus (STN) is an alternative but expensive neurosurgical treatment for parkinsonian patients with levodopa induced motor complications. OBJECTIVE: To assess the safety, clinical effects, quality of life, and economic cost of STN stimulation. METHODS: We conducted a prospective multicentre study in 95 consecutive Parkinson's disease (PD) patients receiving bilateral STN stimulation and assessed its effects over 12 months. A double blind randomised motor evaluation was carried out at 3 month follow up, and quality of life, self care ability, and predictive factors of outcome following surgery were assessed. The cost of PD was estimated over 6 months before and after surgery. RESULTS: The Unified Parkinson's Disease Rating Scale (UPDRS) motor score improved by 57% (p<0.0001) and activities of daily living improved by 48% (p<0.0001) at 12 month follow up. Double blind motor scoring improved by 51% at 3 month follow up (p<0.0001). The total PD Quality of Life Questionnaire (PDQL-37) score improved by 28% (p<0.001). The better the preoperative motor score after a levodopa challenge, the better the outcome after STN stimulation. Five patients developed an intracerebral haematoma during electrode implantation with permanent after effects in two. The 6 month costs of PD decreased from 10,087 euros before surgery to 1673 euros after surgery (p<0.0001) mainly because of the decrease in medication. These savings allowed a return on the procedure investment, estimated at 36,904 euros over 2.2 years. CONCLUSIONS: STN stimulation has good outcomes with relatively low risk and little cost burden in PD patients with levodopa induced motor complications.

Stimulation of the subthalamic nucleus in Parkinson's disease: a 5 year follow up.

BACKGROUND: The short term benefits of bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced levodopa responsive Parkinson's disease (PD) are well documented, but long term benefits are still uncertain. OBJECTIVES: This study provides a 5 year follow up of PD patients treated with stimulation of the STN. METHODS: Thirty seven consecutive patients with PD treated with bilateral STN stimulation were assessed prospectively 6, 24, and 60 months after neurosurgery. Parkinsonian motor disability was evaluated with and without levodopa treatment, with and without bilateral STN stimulation. Neuropsychological and mood assessments included the Mattis Dementia Rating Scale, the frontal score, and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: No severe peri- or immediate postoperative side effects were observed. Six patients died and one was lost to follow up. Five years after neurosurgery: (i) activity of daily living (Unified Parkinson Disease Rating Scale (UPDRS) II) was improved by stimulation of the STN by 40% ("off" drug) and 60% ("on" drug); (ii) parkinsonian motor disability (UPDRS III) was improved by 54% ("off" drug) and 73% ("on" drug); (iii) the severity of levodopa related motor complications was decreased by 67% and the levodopa daily doses were reduced by 58%. The MADRS was unchanged, but cognitive performance declined significantly. Persisting adverse effects included eyelid opening apraxia, weight gain, addiction to levodopa treatment, hypomania and disinhibition, depression, dysarthria, dyskinesias, and apathy. CONCLUSIONS: Despite moderate motor and cognitive decline, probably due to disease progression, the marked improvement in motor function observed postoperatively was sustained 5 years after neurosurgery.

[Gilles de la Tourette syndrome: a self-administered assessment questionnaire]. / Maladie de Gilles de la Tourette. Un auto-questionnaire.

INTRODUCTION: An association of patients with Gilles de la Tourette syndrome enabled us to gather a large body of information regarding the disease manifestations, and patient-perceived consequences. METHOD: 350 questionnaires were sent to patients belonging to the AFSGT (French Association of Patients Suffering from Gilles de la Tourette Syndrome). 187 responses were received (53 percent). The patients were divided into four groups: those with motor tics, vocal tics, complex tics and complex tics with coprolalia. This last group corresponds to the DSM IV definition of "Tourette Disorder". The questions were grouped in five sections: simple manifestations, complex manifestations, family study, treatment and psycho-affective perception (social and in the context of schooling). RESULTS: The study of the simple manifestations of the disorder revealed the homogeneity of the four groups with an age of onset at on average 7 years and a male-to-female ratio of 3.5. The first signs of the disorder are motor tics of the face and neck, and the disorder shows a variable and fluctuating course characterized by periods of decreased or absent symptoms. Familial cases (58 percent) are found in all four groups. The complex signs included in part of behaviors corresponding to the definition of tics: sudden, brusque, repetitive, varied, escape despite efforts to repress them and reappearance more intensely after a period of conscious control. The complex signs also consisted of accompanying factors such as agitation, need to organize, classify or count. Treatments have been of limited success and a significant number of patients have abandoned treatment entirely. Our study demonstrates that this condition seriously affects the daily life of patients, including family and social relations, schooling and occupational life. No patients suffering from transient tics responded to our survey, but such tics were reported in family members. CONCLUSION: Overall, the condition is considered to be single family of disorders, despite the broad phenotypic spectrum, from transitory cases by children to very severe forms. Escape despite efforts to repress tics and the rebound after control tics is characteristic of the Georges Gilles de la Tourette syndrome.

Tourette's syndrome and deep brain stimulation.

In this prospective double blind randomised "N of 1" study, a patient with a severe form of Tourette's syndrome was treated with bilateral high frequency stimulation of the centromedian-parafascicular complex (Ce-Pf) of the thalamus, the internal part of the globus pallidus (GPi), or both. Stimulation of either target improved tic severity by 70%, markedly ameliorated coprolalia, and eliminated self injuries. Severe forms of Tourette's syndrome may benefit from stimulation of neuronal circuits within the basal ganglia, thus confirming the role of the dysfunction of limbic striato-pallido-thalamo-cortical systems in this disorder.

Parkinson disease, brain volumes, and subthalamic nucleus stimulation.

BACKGROUND: High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson disease (PD). The clinical and preoperative predictive factors of the best postoperative outcome have been identified. Radiologic predictive factors were investigated. METHODS: Forty patients with PD underwent surgery for bilateral STN stimulation. MRI was performed in stereotactic conditions before surgery. Brain parenchyma, caudate nucleus, putamen, pallidum, and red nucleus volumes and the surface of the mesencephalon were measured and normalized as percentages of the intracranial volume. Clinical evaluation was performed 1 month before and 6 months after surgery. RESULTS: The normalized brain parenchyma volume was lower in patients who were older and had a longer disease duration or a lower frontal score and was not predictive of the postoperative outcome. The residual scores for activities of daily living and parkinsonian motor disability were higher in patients with a smaller normalized mesencephalon. The normalized caudate nucleus volume was predictive of the pre- and postoperative levodopa-equivalent dosage. CONCLUSIONS: Brain atrophy is not an exclusion criterion for neurosurgery, indicating that patients' neurologic, psychiatric, and neuropsychological characteristics are the best predictive factors for neurosurgery. The fact that a smaller normalized mesencephalon surface was associated with a lower beneficial effect of the subthalamic nucleus stimulation on the parkinsonian motor disability suggests that the normalized mesencephalon surface is a predictive factor of the postoperative outcome.

Does bilateral stimulation of the subthalamic nucleus aggravate apathy in Parkinson's disease?

OBJECTIVE: High frequency stimulation of the subthalamic nucleus (STN) dramatically decreases motor disability in patients with Parkinson"s disease (PD), but has been reported to aggravate apathy. The aim of this study was to analyse the effect of STN stimulation on motivation and reward sensitivity in a consecutive series of PD patients. METHODS: Apathy and reward sensitivity (Apathy Scale, Stimulus-Reward Learning, Reversal, Extinction, and Gambling tasks) were assessed in 18 PD patients treated by bilateral STN stimulation ("on" and "off" conditions) compared with 23 matched patients undergoing long term treatment with levodopa ("on" and "off" conditions). RESULTS: Apathy decreased under both STN stimulation and levodopa treatment, whereas explicit and implicit stimulus reward learning was unchanged. CONCLUSIONS: Bilateral STN stimulation in PD patients does not necessarily have a negative effect on motivation and reward sensitivity and can even improve apathy provided patients have been appropriately selected for neurosurgery.

Neurokinin B, neurotensin, and cannabinoid receptor antagonists and Parkinson disease.

The neuropeptides neurokinin B, neurotensin, and anandamide, the endogenous ligands of NK3, NT1, and CB1 receptors respectively, are known to interact with brain dopaminergic transmission. This study evaluated the effects of these three antagonists of the NK3 (SR 142801), neurotensin (SR 48692), and cannabinoid (SR 141716) receptors on the severity of motor symptoms and levodopa-induced dyskinesias after administration of a single dose of levodopa in 24 patients with Parkinson disease. In this exploratory randomized, double-blind, placebo-controlled study, at the dose used, the drugs tested were well tolerated and could not improve parkinsonian motor disability.

Aggressive behavior induced by intraoperative stimulation in the triangle of Sano.

The authors report a patient with advanced PD, successfully treated by bilateral stimulation of the subthalamic nucleus, who developed acute transient aggressive behavior during intraoperative electrical test stimulation. The electrode responsible for this abnormal behavior was located within the lateral part of the posteromedial hypothalamic region (triangle of Sano). The authors suggest that affect can be dramatically modulated by the selective manipulation of deep brain structures.