Case report: Coexistence of myotonia congenita and Brugada syndrome in one family.

Myotonia congenita is a rare neuromuscular disorder caused by CLCN1 mutations resulting in delayed muscle relaxation. Extramuscular manifestations are not considered to be present in chloride skeletal channelopathies, although recently some cardiac manifestations have been described. We report a family with autosomal dominant myotonia congenita and Brugada syndrome. Bearing in mind the previously reported cases of cardiac arrhythmias in myotonia congenita patients, we discuss the possible involvement of the CLCN1-gene mutations in primary cardiac arrhythmia.

Opposite effects of one session of 1 Hz rTMS on functional connectivity between pre-supplementary motor area and putamen depending on the dyskinesia state in Parkinson's disease.

OBJECTIVE: To explore the effects of low-frequency repetitive transcranial magnetic stimulation (LF rTMS) on cortico-striatal-cerebellar resting state functional connectivity in Parkinson's disease (PD), with and without dyskinesias. METHODS: Because there is increasing evidence of an involvement of the pre-supplementary motor area (pre-SMA) in the pathophysiology of levodopa induced dyskinesias, we targeted the right pre-SMA with LF rTMS in 17 PD patients. We explored the effects of one sham-controlled LF rTMS session on resting state functional connectivity of interconnected brain regions by using functional MRI, and how it is modified by levodopa. The clinical effect on motor function and dyskinesias was documented. RESULTS: As expected, one LF rTMS session did not alleviate dyskinesias. However, real, and not sham LF rTMS significantly increased the functional connectivity with the right putamen in patients with dyskinesias. In patients without dyskinesias, the real LF rTMS session significantly decreased functional connectivity in the right putamen and the cerebellum. We found no effects on functional connectivity after levodopa ingestion. CONCLUSION: One session of 1 Hz rTMS has opposing effects on pre-SMA functional connectivity depending on the PD patients' dyskinesia state. SIGNIFICANCE: Patients dyskinesias state determines the way LF rTMS affects functional connectivity in late stage PD.

Epidemiology of major depression in Belgian parkinsonian patients.

BACKGROUND: Epidemiological data concerning the prevalence of major depression in PD patients in Belgium is very scarce. METHODS: A total of 1086 patients with idiopathic Parkinsons disease were included in the analysis. The neurological evaluation of the patients was made by the Hoehn and Yahr Staging of Parkinsons disease, the Unified Parkinson Disease Rating Scale (UPDRS), and the Schwab and England Activities of Daily Living. The psychiatric evaluation was based on the Mini-International Neuropsychiatric Interview (MINI) and the Montgomery Asberg Depression Rating Scale (MADRS). RESULTS: Based on the MINI questionnaire, the overall proportion of PD patients presenting a current major depressive episode was 15.6%. Interestingly, 30% of all patients included had a history of mood disorder and 46% received either an anxiolytic, an antidepressant or an atypical neuroleptic or a combination of them. The characterisation of the profile of depressed parkinsonian patients shows very few patient's parameters (demographics or motor symptoms) to be associated with a higher risk for major depression. CONCLUSIONS: The PARKIDEP survey confirms a high prevalence of major depression in PD patients in Belgium. A careful follow up of PD patients with a poor functionality, a history of mood disorder or with a complaint of depression or anxiety during the "off" state would help towards a better treatment of the Parkinson's disease associated depression and should improve the quality of life of PD patients.

Treatments for progressing Parkinson's disease: a clinical case scenario study.

OBJECTIVE: A 'case scenario' study on clinical decisions in progressing Parkinson's disease (PD) was developed to complement scientific evidence with the collective judgment of a panel of experts. METHODS: The opinions of 9 experts in movement disorders on the appropriateness of 9 common pharmacological treatments for 33 hypothetical patient profiles were compared to those of 14 general neurologists. Before rating the case scenarios, all participants received a document integrating European and US guidelines for the treatment of patients with advanced PD. Case scenarios showing disagreement or with inconsistencies in appropriateness ratings were discussed at a feedback meeting. A tool for interactive discussion on the clinical case scenarios included was developed based on the outcome of the study. RESULTS: Current guidelines are often insufficient to adequately guide the management of patients with progressing PD. The case scenario study did not reveal major differences in opinions between experts in movement disorders and general neurologists about the appropriateness of certain drug choices for specific case scenarios. However in about 1 out of 5 treatment decisions where experts stated appropriateness or inappropriateness, the general neurologists panel had no or dispersed opinions. CONCLUSIONS: This study reveals more uncertainty about treatment of advanced PD in general neurologists compared with experts in movement disorders and underlines the need for additional support for guiding treatment decisions in clinical practice.

The influence of one session of low frequency rTMS on pre-supplementary motor area metabolites in late stage Parkinson's disease.

OBJECTIVE: To study the effect of Low Frequency repetitive Transcranial Magnetic Stimulation (LF rTMS) on brain metabolites in late stage Parkinson's disease (PD) patients (disease duration at least 4 years and Hoehn and Yahr (1969) score at least 2 in OFF). Several neuroimaging data support a role for pre-Supplementary Motor Area (pre-SMA) involvement in the pathogenesis of Parkinson's disease. Proton magnetic resonance spectroscopy (1H-MRS) measures in vivo metabolites, but results in PD brain remain conflicting and little is known of the effect of LF rTMS thereupon. METHODS: We investigate the neurochemical profile of the right pre-SMA in 17 late stage PD patients (11 male and 6 female, mean age of 71 years) before and after one session of sham controlled 1 Hz rTMS (1000 pulses, 16 minutes), focusing on the tNAA/tCr and tCho/tCr ratios. RESULTS: The tNAA/tCr ratio was unaffected by one session of LF rTMS. We did observe a significant effect of real LF rTMS on the tCho/tCr ratio, inversely correlated with disease duration, and not related to the presence of dyskinesias. As expected, one session of LF rTMS did not affect clinical outcome. CONCLUSIONS: LF rTMS at the right pre-SMA in late stage Parkinson's disease patients does not alter tNAA/tCr, but influences tCho/tCr ratio, in particular in patients with shorter disease duration. SIGNIFICANCE: Pre-SMA LF rTMS seems to influence membrane turnover, more importantly in patients with shorter disease duration. Larger LF rTMS treatment studies applying multiple sessions are needed.

Progressive multifocal leukoencephalopathy as first manifestation of sarcoidosis.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating neurologic disorder caused by a polyomavirus, called JC virus. PML affects mainly immunocompromised hosts. We report a case of PML as first manifestation of sarcoidosis in a previously healthy man. Treatment with cidofovir, resulted in a neurological and radiological stabilization. To our knowledge the association of PML and sarcoidosis without previous immunosuppressive treatment has only been described in a few cases, none of them were treated with cidofovir.

Meningoencephaloradiculitis following infection with tick borne encephalitis virus: case report and review of the literature.

Tick borne encephalitis (TBE) is an infectious zoonotic disease caused by an RNA virus that is endemic to Central and Eastern Europe, Russia, and large parts of Asia. The tick borne encephalitis virus (TBEV) is transmitted through the saliva of infected ticks and infected goat milk. In the vast majority of cases, an infection with TBEV has a subclinical course. However, in some cases, it leads to neurological symptoms due to meningitis, meningoencephalitis, meningoencephalomyelitis, or meningoencephaloradiculitis. Here, we present the first case of meningoencephaloradiculitis in Belgium.

Early-Onset Creutzfeldt-Jakob Disease Mimicking Immune-Mediated Encephalitis.

OBJECTIVES: The objective of this study is to explore the clinical, radiological, and pathological manifestations of a rare subtype of prion disease and their implication for differential diagnosis in case of an early onset neuropsychiatric deterioration. METHODS: We discuss a patients' clinical history, as well as the string of investigations and symptomatological evolution that finally led to a pathological diagnosis. RESULTS: Our patient had the extremely rare VV1 type sporadic Creutzfeldt-Jakob disease (sCJD). We explain the differential diagnosis of progressive encephalomyelitis with rigidity and myoclonus and its implications for treatment. CONCLUSION: sCJD, especially the VV1 subtype, can present at an early age with an insidious psychiatric onset. Classical findings of prion disease-14-3-3 protein, PSWC on electroencephalography, and magnetic resonance imaging patterns-are not always present. The presence of neural autoantibodies does not always implicate pathogenicity in the presence of other neurological/neurodegenerative conditions.

Bilateral low frequency rTMS of the primary motor cortex may not be a suitable treatment for levodopa-induced dyskinesias in late stage Parkinson's disease.

BACKGROUND: In late stage Parkinson patients there is an unmet need for new treatments to adequately control motor complications, especially dyskinesias. In several preliminary studies, it has been suggested that applying unilateral low-frequency repetitive transcranial magnetic stimulation (LF rTMS), delivered at the primary motor cortex (MC) or the supplementary motor area (SMA), may reduce levodopa-induced dyskinesias (LID), either in a single or a multiple session stimulation protocol. In our current clinical research, we examined whether single or multiple (accelerated) sham-controlled bilateral LF rTMS session(s) applied to the primary motor cortices are able to reduce levodopa-induced dyskinesias in patients with advanced Parkinson's disease. METHODS: During a levodopa challenge test, we first investigated the effect of a single sham-controlled session of LF rTMS (1 Hz) to both left and right primary motor cortical areas on dyskinesias and motor function in nine late-stage Parkinson patients. In a second study, patients were assigned to a five day sham-controlled bilateral motor cortex cross-over accelerated LF rTMS protocol and effects on dyskinesias, motor and executive function and emotional status were assessed. RESULTS: We found no significant clinical change in levodopa-induced dyskinesias and motor function with either stimulation protocol. CONCLUSIONS: One or multiple bilateral LF rTMS session(s) applied to the primary motor cortex were unable to reduce levodopa-induced dyskinesias in late-stage Parkinson patients.

Treatment of Parkinson's disease with pergolide and relation to restrictive valvular heart disease.

BACKGROUND: Restrictive valvular heart disease has been reported in patients with Parkinson's disease treated with pergolide. However, few data are available on frequency, severity, dose dependency, and reversibility of pergolide-induced disease, nor on the pulmonary pressures of these patients. We aimed to clarify these characteristics in a large group of patients. METHODS: 78 patients with Parkinson's disease treated with pergolide and 18 never treated with an ergot-derived dopamine agonist (controls) were evaluated by echocardiography. A valvular scoring system was used, ranging from 1 (proven ergot-like restrictive valvular heart disease) to 4 (no disease). For the mitral valve, tenting areas and tenting distances were measured. Systolic pulmonary artery pressures were derived from the tricuspid regurgitant jet. FINDINGS: Restrictive valvular heart disease of any type was present in 26 (33%) patients in the pergolide group and none in controls (p=0.0025). Important disease (score 1 or 2) was present in 15 (19%) patients in the pergolide group and none in controls (p=0.066). Mean tenting distances and tenting areas of the mitral valve were 1.08 cm (range 0.55-2.66) and 2.39 cm2 (0.88-4.59) in the restrictive mitral valve group versus 0.63 cm (0.22-1.20) and 1.39 cm2 (0.39-3.23) in the non-restrictive group (p=0.003 and p<0.0001, respectively). Significant correlation was noted between cumulative doses of pergolide and tenting areas of the mitral valves (r=0.412, p=0.017). Mean systolic pulmonary artery pressures were 39.3 mm Hg (range 25-71) in the high-dose group versus 38.5 mm Hg (20-65) in the low-dose group (p=0.76) and 31 mm Hg (25-40) in controls (p=0.02 vs all patients given pergolide). In six patients, pergolide treatment was stopped because of restrictive valvular heart disease, in two of whom regression of disease was shown. INTERPRETATION: Restrictive valvular heart disease is not a rare finding in patients treated with pergolide. Clinicians should consider changing to a non-ergot drug if this disease is diagnosed.

Delayed akinetic catatonic mutism following methadone overdose.

A 49-year-old woman developed a catatonic mute state a few weeks after methadone overdose. Clinical, radiological and histological findings were consistent with toxic spongiform leukoencephalopathy, which adds a potentially deadly side-effect to a generally considered safe substitution for heroin.

Fatigue as the presenting symptom of chronic inflammatory demyelinating polyneuropathy.

Different clinical presentations of chronic inflammatory demyelinating polyneuropathy (CIDP) have been described. Fatigue is generally considered to be a secondary sign and is not mentioned as a warning sign for the diagnosis. We present a patient with CIDP in whom fatigue remained the only symptom, hereby stressing the importance of adding this disease to the differential diagnosis of fatigue. Immunomodulatory treatment did not change the clinical course of the patient, but electrodiagnostic features improved substantially.