A multicenter double-blind randomized crossover study comparing the impact of dorsal subthalamic nucleus deep brain stimulation versus standard care on apathy in Parkinson's disease: a study protocol.

BACKGROUND: Neuroimaging studies suggest an association between apathy after deep brain stimulation (DBS) and stimulation of the ventral part of the subthalamic nucleus (STN) due to the associative fibers connected to the non-motor limbic circuits that are involved in emotion regulation and motivation. We have previously described three patients with severe apathy that could be fully treated after switching stimulation from a ventral electrode contact point to a more dorsal contact point. OBJECTIVES: To determine whether more dorsal stimulation of the STN decreases apathy compared to standard care in a multicenter randomized controlled trial with a crossover design. METHODS: We will include 26 patients with a Starkstein Apathy Scale (SAS) score of 14 or more after subthalamic nucleus (STN) deep brain stimulation (DBS) for refractory Parkinson's disease. This is a multicenter trial conducted in two teaching hospitals and one university medical center in the Netherlands after at least 3 months of STN DBS. Our intervention will consist of 1 month of unilateral dorsal STN stimulation compared to treatment as usual. The primary outcome is a change in SAS score following 1 month of DBS on the original contact compared to the SAS score following 1 month of DBS on the more dorsal contact. Secondary outcomes are symptom changes on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale motor part III, Montgomery-Åsberg Depression Rating Scale, 39-item Parkinson's disease questionnaire, Parkinson's disease impulsive-compulsive disorders questionnaire, changes in levodopa-equivalent daily dosage, apathy rated by the caregiver, and burden and quality of life of the caregiver. TRIAL REGISTRATION: ClinicalTrials.gov NL8279. Registered on January 10, 2020.

Nitrous-oxide-induced polyneuropathy and subacute combined degeneration of the spine: clinical and diagnostic characteristics in 70 patients, with focus on electrodiagnostic studies.

BACKGROUND AND PURPOSE: Nitrous oxide (N2 O) induced neurological symptoms are increasingly encountered. Our aim is to provide clinical and diagnostic characteristics with a focus on electrodiagnostic studies. METHODS: Patients with neurological sequelae due to N2 O presenting in our hospital between November 2018 and December 2021 reporting clinical and diagnostic data were retrospectively reviewed. RESULTS: Seventy patients (median 22 years) were included. Median N2 O usage was 4 kg/week during 12 months. Patients' history revealed a higher rate of sensory symptoms compared to motor (97% vs. 57%) and 77% walking difficulties. Clinical diagnosis was polyneuropathy (PNP) in 44%, subacute combined degeneration (SCD) of the spine in 19%, both in 37%. Median vitamin B12 level was low (159 pmol/L), normal in 16%. The median methylmalonic acid was increased (2.66 µmol/L). Electrodiagnostic abnormalities were observed in 91%, with 72% fulfilling axonal PNP criteria, 20% showing mild to intermediate slowing. One patient fulfilled demyelinating PNP criteria not related to N2 O abuse (Charcot-Marie-Tooth type 1a). More prominent motor nerve conduction abnormalities were found; lower limbs were more affected. In 64% with normal conduction, myography showed signs of axonal loss. Magnetic resonance imaging showed cervical myelopathy in 58% involving generally five to six segments. CONCLUSIONS: Nitrous oxide (N2 O) leads to neurological symptoms by causing PNP and/or SCD primarily involving the legs. Distinguishing PNP and SCD clinically was shown to be insufficient. Electrodiagnostic studies showed axonal PNP. Demyelinating PNP due to N2 O abuse was not present in our cohort. Therefore, further diagnostic work-up is warranted if demyelinating features are present.

Two cases with postural axial tremor: Consider a genetic origin.

We present two cases with postural axial tremor predominantly involving the head, trunk, and shoulders. In the first patient, the postural tremor occurred in multiple attacks a day lasting approximately 10 min. The second patient developed a progressive tremor of his head and arms, worsened during sitting and standing. Electrophysiological supported the postural axial tremor in both patients with a varying 3-10 Hz tremor frequency between different muscles and within the same muscles at different times. Postural axial tremor is a rare and complex movement disorder. The majority of cases are caused by acquired cerebellar pathology. However, isolated cases with underlying genetic disorders are described in literature. Here, we illustrate how to differentiate paroxysmal axial tremor from other axial hyperkinetic movement disorders and extend the genetic heterogeneity of this intriguing movement disorder phenotype.

Tremor and myoclonus.

Tremor and myoclonus are two common hyperkinetic movement disorders. Tremor is characterized by rhythmic oscillatory movements while myoclonic jerks are usually arrhythmic. Tremor can be classified into subtypes including the most common types: essential, enhanced physiological, and parkinsonian tremor. Myoclonus classification is based on its anatomic origin: cortical, subcortical, spinal, and peripheral myoclonus. The clinical presentations are unfortunately not always classic and electrophysiologic investigations can be helpful in making a phenotypic diagnosis. Video-polymyography is the main technique to (sub)classify the involuntary movements. In myoclonus, advanced electrophysiologic testing, such as back-averaging, coherence analysis, somatosensory-evoked potentials, and the C-reflex can be of additional value. Recent developments in tremor point toward a role for intermuscular coherence analysis to differentiate between tremor subtypes. Classification of the movement disorder based on clinical and electrophysiologic features is important, as it enables the search for an etiological diagnosis and guides tailored treatment.

Improving neurophysiological biomarkers for functional myoclonic movements.

INTRODUCTION: Differentiating between functional jerks (FJ) and organic myoclonus can be challenging. At present, the only advanced diagnostic biomarker to support FJ is the Bereitschaftspotential (BP). However, its sensitivity is limited and its evaluation subjective. Recently, event related desynchronisation in the broad beta range (13-45 Hz) prior to functional generalised axial (propriospinal) myoclonus was reported as a possible complementary diagnostic marker for FJ. Here we study the value of ERD together with a quantified BP in clinical practice. METHODS: Twenty-nine patients with FJ and 16 patients with cortical myoclonus (CM) were included. Jerk-locked back-averaging for determination of the 'classical' and quantified BP, and time-frequency decomposition for the event related desynchronisation (ERD) were performed. Diagnostic gain, sensitivity and specificity were obtained for individual and combined techniques. RESULTS: We detected a classical BP in 14/29, a quantitative BP in 15/29 and an ERD in 18/29 patients. At group level we demonstrate that ERD in the broad beta band preceding a jerk has significantly higher amplitude in FJ compared to CM (respectively -0.14 ± 0.13 and +0.04 ± 0.09 (p < 0.001)). Adding ERD to the classical BP achieved an additional diagnostic gain of 53%. Furthermore, when combining ERD with quantified and classical BP, an additional diagnostic gain of 71% was achieved without loss of specificity. CONCLUSION: Based on the current findings we propose to the use of combined beta ERD assessment and quantitative BP analyses in patients with a clinical suspicion for all types of FJ with a negative classical BP.

The presence of depression and anxiety do not distinguish between functional jerks and cortical myoclonus.

INTRODUCTION: Functional movement disorders are accompanied by a high occurrence of psychopathology and cause serious impairments in quality of life. However, little is known about this in patients with functional jerks and no comparison has been made between patients with functional jerks and organic myoclonus. This case control study compares the occurrence of depression, anxiety and quality of life (HR-QoL) in patients with functional jerks and cortical myoclonus. METHODS: Patients with functional jerks and cortical myoclonus, consecutively recruited, were compared on self-rated anxiety (Beck Anxiety Inventory), depression (Beck Depression Inventory), health-related quality of life (RAND-36), and myoclonus severity (UMRS and CGI-S rating scales). RESULTS: Sixteen patients with functional jerks and 23 with cortical myoclonus were evaluated. There was no significant difference in depression (44% vs. 43%) or anxiety (44% vs. 47%) scores between groups. The HR-QoL was similarly impaired except that functional jerks patients reported significantly more pain (p < 0.05). Only in the functional jerks group myoclonus severity correlated with depression and anxiety. CONCLUSION: Depression and anxiety scores are high and do not discriminate between functional jerks and cortical myoclonus. Quality of life was equally impaired in both sub-groups, but pain was significantly worse in patients with functional jerks.

Clinical characterization of dystonia in adult patients with Huntington's disease.

BACKGROUND AND PURPOSE: Huntington's disease (HD) is an autosomal dominant, neurodegenerative movement disorder, typically characterized by chorea. Dystonia is also recognized as part of the HD motor phenotype, although little work detailing its prevalence, distribution, severity and impact on functional capacity has been published to date. METHODS: Patients (>18 years of age) were recruited from the Cardiff (UK) HD clinic, each undergoing a standardized videotaped clinical examination and series of functional assessment questionnaires (Unified Huntington's Disease Rating Scale, Burke-Fahn-Marsden Dystonia Rating Scale and modified version of the Toronto Western Spasmodic Torticollis Rating Scale). The presence and severity of dystonia were scored by four independent neurologists using the Burke-Fahn-Marsden Dystonia Rating Scale and Unified Huntington's Disease Rating Scale. Statistical analysis included Fisher's exact test, Wilcoxon test, anova and calculation of correlation coefficients where appropriate. RESULTS: Forty-eight patients [91% (48/53)] demonstrated evidence of dystonia, with the highest prevalence in the left upper limb (n = 44, 83%), right upper limb most severely affected and eyes least affected. Statistically significant positive correlations (P < 0.05) were observed between dystonia severity and increasing HD disease stage and motor disease duration. Deterioration in functional capacity also correlated with increasing dystonia severity. No significant relationship was observed with age at motor symptom onset or CAG repeat length. CONCLUSIONS: We report a high prevalence of dystonia in adult patients with HD, with worsening dystonia severity with increasing HD disease stage and motor disease duration. The recognition and management of dystonic symptoms in routine clinical practice will aid overall symptomatic treatment and functional improvement.

Myoclonus subtypes in tertiary referral center. Cortical myoclonus and functional jerks are common.

OBJECTIVE: To evaluate the accuracy of clinical phenotyping of myoclonus patients and to determine differentiating clinical characteristics between cortical (CM), subcortical (SCM), spinal (SM), peripheral (PM) myoclonus, and functional jerks (FJ). METHODS: Clinical notes for all patients with myoclonus over an 8-year period (2006-2014) were reviewed retrospectively. We used the conclusion of electrophysiological testing as definite diagnosis of myoclonus or FJ. RESULTS: 85 patients were identified suffering from CM (34%), SCM (11%), SM (6%), PM (2%), and 47% FJ. The clinical diagnosis of myoclonus was confirmed by electrophysiological testing in 74% and its subtype in 78% of cases. CM was characterized by an early age of onset, facial myoclonus, and provocation by action. Differentiating features of FJ were an abrupt onset, preceding contributing events and provocation by a supine position. CONCLUSION: The majority of clinical myoclonic jerk cases were functional in our heterogeneous tertiary clinic cohort. CM was the main anatomical myoclonic subtype. Clinical diagnosis was accurate in the majority of cases, although electrophysiological testing was important to verify the clinical classification. SIGNIFICANCE: In patients with jerky movements a functional diagnosis should be considered. Determination of the myoclonic subtypes is important to initiate tailored treatment.

Rhabdomyolysis: review of the literature.

Rhabdomyolysis is a serious and potentially life threatening condition. Although consensus criteria for rhabdomyolysis is lacking, a reasonable definition is elevation of serum creatine kinase activity of at least 10 times the upper limit of normal followed by a rapid decrease of the sCK level to (near) normal values. The clinical presentation can vary widely, classical features are myalgia, weakness and pigmenturia. However, this classic triad is seen in less than 10% of patients. Acute renal failure due to acute tubular necrosis as a result of mechanical obstruction by myoglobin is the most common complication, in particular if sCK is >16.000 IU/l, which may be as high as 100,000 IU/l. Mortality rate is approximately 10% and significantly higher in patients with acute renal failure. Timely recognition of rhabdomyolysis is key for treatment. In the acute phase, treatment should be aimed at preserving renal function, resolving compartment syndrome, restoring metabolic derangements, and volume replacement. Most patients experience only one episode of rhabdomyolysis, mostly by substance abuse, medication, trauma or epileptic seizures. In case of recurrent rhabdomyolysis, a history of exercise intolerance or a positive family history for neuromuscular disorders, further investigations are needed to identify the underlying, often genetic, disorder. We propose a diagnostic algorithm for use in clinical practice.