Johannes H.T.M. Koelman

Objective: To explore changes in resting-state networks in patients with jerky and tremulous functional movement disorders (JT-FMD). Methods: Resting-state fMRI data from seventeen patients with JT-FMD and seventeen age-, sex-, and education matched healthy controls was investigated. Independent component analysis was used to examine the frontoparietal network (FPN), dorsal attention network (DAN), salience network (SN), and default mode network (DMN). Frequency distribution of network signal fluctuations, intra- and internetwork functional connectivity were investigated. Symptom severity was measured using the Clinical Global Impression-Severity scale. Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) scores were collected to measure depression and anxiety in FMD, respectively. Results: Compared with healthy controls, patients with JT-FMD had significantly decreased power of lower-range (0.01-0.10 Hz) frequency fluctuations in a precuneus and posterior cingulate cortex (PCC) component of the DMN, and in the DAN component (FDR-corrected P<0.05). No significant group differences were found for intra- and internetwork functional connectivity. In patients with JT-FMD, symptom severity was not significantly correlated with network measures. Depression scores were weakly correlated with intranetwork functional connectivity in the medial prefrontal cortex, while anxiety was not found to be related to network connectivity. Conclusions: Given the changes in the postero-dorsal components of the DMN and DAN, we postulate that the JT-FMD-related functional alterations found in these regions could provide support for the concept that particularly impaired attentional control is a fundamental disturbance in these patients.

Botulinum toxin (BoNT) injections in the dystonic muscles is the preferred treatment for Cervical Dystonia (CD), but the proper identification of the dystonic muscles remains a challenge. Previous studies showed decreased 8–14 Hz autospectral power in the electromyography (EMG) of splenius muscles in CD patients. Cumulative distribution functions (CDF’s) of dystonic muscles showed increased CDF₁₀ values, representing increased autospectral powers between 3 and 10 Hz, relative to power between 3 and 32 Hz. In this study, we evaluated both methods and investigated the effects of botulinum toxin. Intramuscular EMG recordings were obtained from the splenius, semispinalis, and sternocleidomastoid muscles during standardized isometric tasks in 4 BoNT-naïve CD patients, 12 BoNT-treated patients, and 8 healthy controls. BoNT-treated patients were measured 4–7 weeks after their last BoNT injections and again after 11–15 weeks. We found significantly decreased 8–14 Hz autospectral power in splenius muscles, but not in the semispinalis and sternocleidomastoid muscles of CD patients when compared to healthy controls. CDF₁₀ analysis was superior in demonstrating subtle autospectral changes, and showed increased CDF₁₀ values in all studied muscles of CD patients. These results did not change significantly after BoNT injections. Further studies are needed to investigate the origin of these autospectral changes in dystonia patients, and to assess their potential in muscle selection for BoNT treatment.

Niemann-Pick type C (NP-C) is a rare autosomal recessive progressive neurodegenerative disorder caused by mutations in the NP-C 1 or 2 gene. Besides visceral symptoms, presentation in adolescent and adult onset variants is often with neurological symptoms. The most frequently reported presenting symptoms of NP-C in adulthood are psychiatric symptoms (38 %), cognitive decline (23 %) and ataxia (20 %). Myoclonus can be present, but its value in early diagnosis and the evolving clinical phenotype in NP-C is unclear. In this paper we present eight Dutch cases of NP-C of whom five with myoclonus. Eight patients with genetically confirmed NP-C were recruited from two Dutch University Medical Centers. A structured interview and neuropsychological tests (for working and verbal memory, attention and emotion recognition) were performed. Movement disorders were assessed using a standardized video protocol. Quality of life was evaluated by questionnaires (Rand-36, SIP-68, HAQ). In four of the five patients with myoclonic jerks simultaneous EEG with EMG was performed. A movement disorder was the initial neurological symptom in six patients: three with myoclonus and three with ataxia. Two others presented with psychosis. Four experienced cognitive deficits early in the course of the disease. Patients showed cognitive deficits in all investigated domains. Five patients showed myoclonic jerks, including negative myoclonus. In all registered patients EEG-EMG coherence analysis and/or back-averaging proved a cortical origin of myoclonus. Patients with more severe movement disorders experienced significantly more physical disabilities. Presenting neurological symptoms of NP-C include movement disorders, psychosis and cognitive deficits. At current neurological examination movement disorders were seen in all patients. The incidence of myoclonus in our cohort was considerably higher (63 %) than in previous publications and it was the presenting symptom in 38 %. A cortical origin of myoclonus was demonstrated. Our data suggest that myoclonus may be overlooked in patients with NP-C. All patients scored significantly lower on physical domains of HRQoL. Symptomatic treatment of movement disorders may improve physical functioning and subsequently HRQoL.

Background: To describe the neurologic profiles of Rhizomelic chondrodysplasia punctata (RCDP); a peroxisomal disorder clinically characterized by skeletal abnormalities, congenital cataracts, severe growth and developmental impairments and immobility of joints. Defective plasmalogen biosynthesis is the main biochemical feature. Methods: Observational study including review of clinical and biochemical abnormalities, genotype, presence of seizures and neurophysiological studies of a cohort of 16 patients with RCDP. Results: Patients with the severe phenotype nearly failed to achieve any motor or cognitive skills, whereas patients with the milder phenotype had profound intellectual disability but were able to walk and had verbal communication skills. Eighty-eight percent of patients developed epileptic seizures. The age of onset paralleled the severity of the clinical and biochemical phenotype. Myoclonic jerks, followed by atypical absences were most frequently observed. All patients with clinical seizures had interictal encephalographic evidence of epilepsy. Visual evoked (VEP) and brain auditory potential (BAEP) studies showed initial normal latency times in 93% of patients. Deterioration of VEP occurred in a minority in both the severe and the milder phenotype. BAEP and somatosensory evoked potentials (SSEP) were more likely to become abnormal in the severe phenotype. Plasmalogens were deficient in all patients. In the milder phenotype levels of plasmalogens were significantly higher in erythrocytes than in the severe phenotype. Phytanic acid levels ranged from normal to severely increased, but had no relation with the neurological phenotype. Conclusion: Neurodevelopmental deficits and age-related occurrence of seizures are characteristic of RCDP and are related to the rest-activity in plasmalogen biosynthesis. Evoked potential studies are more likely to become abnormal in the severe phenotype, but are of no predictive value in single cases of RCDP.

Acute posthypoxic myoclonus (PHM) can occur in patients admitted after cardiopulmonary resuscitation (CPR) and is considered to have a poor prognosis. The origin can be cortical and/or subcortical and this might be an important determinant for treatment options and prognosis. The aim of the study was to investigate whether acute PHM originates from cortical or subcortical structures, using somatosensory evoked potential (SEP) and electroencephalogram (EEG).

Background Tremor is the most prevalent movement disorder in clinical practice. It is defined as involuntary, rhythmic, oscillatory movements. The diagnostic process of patients with tremor can be laborious and challenging, and a clear, systematic overview of available diagnostic techniques is lacking. Tremor can be a symptom of many diseases, but can also represent a distinct disease entity. Objective The objective of this review is to give a clear, systematic and step-wise overview of the diagnostic work-up of a patient with tremor. The clinical relevance and value of available laboratory tests in patients with tremor will be explored. Methods We systematically searched through EMBASE. The retrieved articles were supplemented by articles containing relevant data or provided important background information. Studies that were included investigated the value and/or usability of diagnostic tests for tremor. Results In most patients, history and clinical examination by an experienced movement disorders neurologist are sufficient to establish a correct diagnosis, and further ancillary examinations will not be needed. Ancillary investigation should always be guided by tremor type(s) present and other associated signs and symptoms. The main ancillary examination techniques currently are electromyography and SPECT imaging. Unfortunately, many techniques have not been studied in large prospective, diagnostic studies to be able to determine important variables like sensitivity and specificity. Conclusion When encountering a patient with tremor, history and careful clinical examination should guide the diagnostic process. Adherence to the diagnostic work-up provided in this review will help the diagnostic process of these patients.

Background: Short latency somatosensory evoked potential (SSEP) (N20) is a good predictor of poor outcome in postanoxic coma. It has been suggested that the long latency response (N70) may increase the sensitivity of SSEPs for predicting poor outcome. Methods: As part of a prospective cohort study in 407 adult patients unconscious 24 hours after cardiopulmonary resuscitation (CPR), N20 was recorded 24, 48, and 72 hours after CPR, and N70 was recorded at least once in 319 patients. Poor outcome was defined as death or persistent vegetative state 1 month after CPR. Results: Absent N20 had a 0% false positive test rate at all time intervals, with prevalence of poor test result varying from 37 to 48%. Addition of abnormal N70 (absent or delayed > 130 msec) with present N20 as poor test result added 21 to 28% to this prevalence, but at the cost of a false positive test rate of 4 to 15%. Good outcome could not be predicted reliably with either of the tests, as only 28% of patients with normal N20 and N70 had a good outcome. Conclusion: Determination of presence or absence of the N70 in patients with postanoxic coma gives additional information about the likelihood of poor outcome, but it is not precise enough to base treatment decisions solely on its absence.