Tremor in motor neuron disease may be central rather than peripheral in origin

BACKGROUND AND PURPOSE: Motor neuron disease (MND) refers to a spectrum of degenerative diseases affecting motor neurons. Recent clinical and post-mortem observations have revealed considerable variability in the phenotype. Rhythmic involuntary oscillations of the hands during action, resembling tremor, can occur in MND, but their pathophysiology has not yet been investigated. METHODS: A total of 120 consecutive patients with MND were screened for tremor. Twelve patients with action tremor and no other movement disorders were found. Ten took part in the study. Tremor was recorded bilaterally using surface electromyography (EMG) and triaxial accelerometer, with and without a variable weight load. Power spectra of rectified EMG and accelerometric signal were calculated. To investigate a possible cerebellar involvement, eyeblink classic conditioning was performed in five patients. RESULTS: Action tremor was present in about 10% of our population. All patients showed distal postural tremor of low amplitude and constant frequency, bilateral with a small degree of asymmetry. Two also showed simple kinetic tremor. A peak at the EMG and accelerometric recordings ranging from 4 to 12 Hz was found in all patients. Loading did not change peak frequency in either the electromyographic or accelerometric power spectra. Compared with healthy volunteers, patients had a smaller number of conditioned responses during eyeblink classic conditioning. CONCLUSIONS: Our data suggest that patients with MND can present with action tremor of a central origin, possibly due to a cerebellar dysfunction. This evidence supports the novel idea of MND as a multisystem neurodegenerative disease and that action tremor can be part of this condition

Deconstructing Fahr's disease/syndrome of brain calcification in the era of new genes

Introduction There are now a number genes, known to be associated with familial primary brain calcification (PFBC), causing the so called ‘Fahr's’ disease or syndrome. These are SCL20A2, PDGFB, PDGFRB and XPR1. In this systematic review, we analyse the clinical and radiological features reported in genetically confirmed cases with PFBC. We have additionally reviewed pseudohypoparathyroidism which is a close differential diagnosis of PFBC in clinical presentation and is also genetically determined. Methods We performed a Medline search, from 1st Jan 2012 through to 7th November 2016, for publications with confirmed mutations of SCL20A2, PDGFB, PDGFRB, and XPR1 and found twenty papers with 137 eligible cases. A second search was done for publications of cases with Pseudohypoparathyroidism or pseudopseudohypoparathyroidism, and found 18 publications with 20 eligible cases. Results SLC20A2 was the most common gene involved with 75 out of 137 cases included with PFBC (55%) followed by PDGFB (31%) and PDGFRB (11%). Statistically significant correlation was found between the presence of parkinsonism with SLC20A2 mutations, headache in PDGFB and generalised tonic-clonic seizures in patients with pseudohypoparathyroidism. Conclusion We combine statistical analysis and clinical inference to suggest a diagnostic algorithm based on the observations in this study to help with investigation of a patient with neurological features and brain calcification

Dystonia: A review

Dystonia is a hyperkinetic movement disorder characterized by sustained or intermittent muscle contractions that cause abnormal repetitive movements, abnormal postures, or both. The new consensus classifies dystonia into two axes to characterize clinical characteristics, and etiology. This system allows correct identification of isolated and combined forms of dystonia and retains the description of generalized and focal dystonia which is very useful in planning investigations and management. The characterization of dystonia for its better identification and a brief overview of its management are discussed in this article. The treatment options for dystonia include drugs, botulinum toxin and deep brain stimulation surgery

Dystonic opisthotonus: A "red flag" for neurodegeneration with brain iron accumulation syndromes?

Back arching was reported in one of the very first patients with neurodegeneration with brain iron accumulation syndrome (NBIAs) published in 1936. However, recent reports have mainly focused on the genetic and imaging aspects of these disorders, and the phenotypic characterization of the dystonia has been lost. In evaluating patients with NBIAs in our centers, we have observed that action-induced dystonic opisthotonus is a common and characteristic feature of NBIAs. Here, we present a case series of patients with NBIAs presenting this feature demonstrated by videos. We suggest that dystonic opisthotonus could be a useful "red flag" for clinicians to suspect NBIAs, and we discuss the differential diagnosis of this feature. This would be particularly useful in identifying patients with NBIAs and no iron accumulation as yet on brain imaging (for example, as in phospholipase A2, group IV (cytosolic, calcium-independent) [PLA2G6]-related disorders), and it has management implications.© 2013 International Parkinson and Movement Disorder Society

Exploratory pilot study exploring clinical effects of exogenous sustained-release Melatonin on nocturia in Parkinson’s Disease

Introduction: Nocturia is one of the commonest non‐motor symptoms in Parkinson’s disease (PD). Nocturia has evolved from being understood as a symptom of urological disorders or neurogenic bladder dysfunction to being considered as a form of circadian dysregulation. Exogenous melatonin is known to help circadian function and can be an effective strategy for nocturia in PD. Methods: In this open label single‐site exploratory phase 2 pilot study, adults with PD and nocturia underwent assessments using standardised questionnaires, urodynamics studies and a bladder scan. This was followed by completion of a frequency volume charts (FVC) and two weeks sleep diary. Sustained‐release melatonin 2mg was then administered once nightly for six weeks. A repeat assessment using questionnaires, the FVC and sleep diary was performed whilst on treatment with melatonin. Companion or bed partners filled in sleep questionnaires to assess their sleep during the intervention. Results: 20 patients (12 males; mean 68.2 (SD=7.8) years; mean PD duration 8.0 (±5.5) years with PD reporting nocturia were included. Administration of melatonin was associated with a significant reduction in the primary outcome bother related to nocturia measured using the International Consultation on Incontinence Questionnaire Nocturia (ICIQ‐N) (p=0.01), number of episodes of nocturia per night (p=0.013) and average urine volume voided at night (p=0.013). No serious adverse events were reported. No significant improvement was noted in bed‐partner sleep scores. Conclusion: In this preliminary open‐label study, administration of sustained‐release melatonin 2mg was found to be safe for clinical use and was associated with significant improvements in night‐time frequency and nocturnal voided volumes in PD patients

Neurodegeneration with brain iron accumulation

The term NBIA encompasses a heterogeneous group of inherited disorders characterized clinically by progressive extra pyramidal syndrome and pathologically by excessive iron deposition in brain, primarily affecting the basal ganglia (globus pallidus mainly).The hallmark of this syndrome is the age specific phenotypic presentation and intraphenotypic heterogeneity. NBIAs at present include ten subtypes with genes identified in nine subtypes. They form an important differential diagnosis for the phenotype of global developmental delay in infancy/childhood to dystonia-parkinsonism or isolated parkinsonism at all ages and also for the isolated craniocervical dystonia of adult onset. There needs to be a high index of clinical suspicion for this syndrome and the evaluation includes MRI brain T2∗ weighted imaging which reveal symmetrical iron deposition in bilateral globus pallidi and other basal ganglia. The T2 ∗ imaging pattern of iron deposition varies amongst the different subtypes and the combination of clinical phenotype and MRI signature makes it easier to confidently make a diagnosis of NBIA and to recommend genetic testing. The treatment to date is mostly symptomatic with targeted therapies on the horizon

Lower urinary tract dysfunction in Parkinsonian syndromes

Purpose of review: The aim of this review is to outline the clinical presentation, pathophysiology and evaluation of lower urinary tract (LUT) dysfunction in Parkinson’s disease and other parkinsonian syndromes including multiple system atrophy, dementia with Lewy bodies, progressive supranuclear palsy and corticobasal degeneration. // Recent findings: LUT dysfunction commonly occurs in neurological disorders, including patients with parkinsonian syndromes. The pattern of LUT dysfunction and its severity are variable, depending upon the site of lesion within the neural pathways. Parkinsonian syndromes are broadly divided into Parkinson’s disease (PD) and a typical parkinsonian syndromes such as multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Different parkinsonian syndromes have distinct clinical features (e.g. dysautonomia, early dementia, supranuclear gaze palsy, higher cortical signs), and the pattern of LUT dysfunction and its severity can differ. // Conclusions: LUT dysfunction is a common feature in patients with parkinsonian syndromes. Recognising the pattern of LUT dysfunction during the assessment of these patients can help management and possibly facilitate an earlier diagnosis

Multidisciplinary treatment for functional neurological symptoms: a prospective study.

Although functional neurological symptoms are often very disabling there is limited information on outcome after treatment. Here we prospectively assessed the short- and long-term efficacy of an inpatient multidisciplinary programme for patients with FNS. We also sought to determine predictors of good outcome by assessing the responsiveness of different scales administered at admission, discharge and follow-up. Sixty-six consecutive patients were included. Assessments at admission, discharge and at 1 year follow-up (55%) included: the Health of the Nation Outcome Scale, the Hospital Anxiety and Depression Scale, the Patient Health Questionnaire-15, the Revised Illness Perception Questionnaire, the Common Neurological Symptom Questionnaire, the Fear Questionnaire and the Canadian Occupational Performance Measure. At discharge and at 1 year follow-up patients were also asked to complete five-point self-rated scales of improvement. There were significant improvements in clinician-rated mental health and functional ability. In addition, patients reported that their levels of mood and anxiety had improved and that they were less bothered by somatic symptoms in general and neurological symptoms in particular. Two-thirds of patients rated their general health such as "better" or "much better" at discharge and this improvement was maintained over the following year. Change in HoNOS score was the only measure that successfully predicted patient-rated improvement. Our data suggest that a specialized multidisciplinary inpatient programme for FNS can provide long-lasting benefits in the majority of patients. Good outcome at discharge was exclusively predicted by improvement in the HoNOS which continued to improve over the 1 year following discharge