The clinical spectrum and pathophysiology of neuropathic tremor

This thesis describes a series of studies involving patients with neuropathies and healthy controls. In the studies of disease, two groups were recruited: patients with inflammatory neuropathies and those with hereditary neuropathies. Each group was separated into those with and those without tremor and compared with healthy controls. Clinical assessments and neurophysiological tests were employed to correlate cerebellar function with tremor. The final study of healthy participants investigated the effect of transcranial direct current stimulation (TDCS) on the cerebellum during finger tapping. 1) Tremor was most common in IgM paraproteinaemic neuropathies, also occurring in 58% of those with chronic inflammatory demyelinating polyradiculoneuropathy and 56% of those with multifocal motor neuropathy with conduction block (MMNCB). Tremor was generally refractory to treatment and contributed to disability in some patients. Although tremor severity correlated with F wave latency, it was insufficient to distinguish those with, from those without tremor. 2) Impaired eyeblink classical conditioning and paired associative stimulation in patients with inflammatory neuropathy and tremor differentiated them from neuropathy patients without tremor and healthy controls, strongly suggesting impairment of cerebellar function is linked to the production of tremor in these patients. 3) The prevalence study in CMT1A patients revealed tremor in 21% and in 42% of those it caused impairment. Eyeblink conditioning, visuomotor adaptation and electro-oculography were no different between tremulous and non-tremulous patients and healthy controls. This argues against a prominent role for an abnormal cerebellum in tremor generation in the patients studied. Rather, they suggest an enhancement of the central neurogenic component of physiological tremor as a possible mechanism. 4) TDCS of the lateral cerebellum and its effect on paced finger tapping was examined. There was no effect on accuracy or variability of the intertap interval, providing no support for a direct role of the cerebellum in event based timing

Susac syndrome presenting with acute hemibody paraesthesia

Susac syndrome is an orphan disease characterised by encephalopathy, branch retinal artery occlusion and sensorineural hearing loss. As the clinical triad is rarely present at symptom onset, it is often initially misdiagnosed and appropriate treatment is often delayed. Herewith, we report a case of Susac syndrome in a 47-year-old man presenting with acute hemisensory loss and highlight the challenges of early diagnosis, particularly relevant in the era of hyperacute stroke management

Psychogenic palatal tremor may be underrecognized: reappraisal of a large series of cases.

Palatal tremor is characterized by rhythmic movements of the soft palate and can be essential or symptomatic. Some patients can have palatal movements as a special skill or due to palatal tics. Psychogenic palatal tremor is recognized but rarely reported in the literature

Moving toward "laboratory-supported" criteria for psychogenic tremor.

A confident clinical diagnosis of psychogenic tremor is often possible, but, in some cases, a "laboratory-supported" level of certainty would aid in early positive diagnosis. Various electrophysiological tests have been suggested to identify patients with psychogenic tremor, but their diagnostic reliability has never been assessed "head to head" nor compared to forms of organic tremor other than essential tremor or PD. We compared baseline tremor characteristics (e.g., frequency and amplitude) as well as electrophysiological tests previously reported to distinguish psychogenic and organic tremor in a cohort of 13 patients with psychogenic tremor and 25 patients with organic tremor, the latter including PD, essential-, dystonic-, and neuropathic tremors. We assessed between-group differences and calculated sensitivity and specificity for each test. A number of tests, including entrainment or frequency changes with tapping, pause of tremor during contralateral ballistic movements, increase in tremor amplitude with loading, presence of coherence, and tonic coactivation at tremor onset, revealed significant differences on a group level, but there was no single test with adequate sensitivity and specificity for separating the groups (33%-77% and 84%-100%, respectively). However, a combination of electrophysiological tests was able to distinguish psychogenic and organic tremor with excellent sensitivity and specificity. A laboratory-supported level of diagnostic certainty in psychogenic tremor is likely to require a battery of electrophysiological tests to provide sufficient specificity and sensitivity. Our data suggest such a battery that, if supported in a prospective study, may form the basis of laboratory-supported criteria for the diagnosis of psychogenic tremor

Rest and other types of tremor in adult-onset primary dystonia

Knowledge regarding tremor prevalence and phenomenology in patients with adult-onset primary dystonia is limited. Dystonic tremor is presumably under-reported, and we aimed to assess the prevalence and the clinical correlates of tremor in patients with adult-onset primary dystonia

Normal motor adaptation in cervical dystonia: a fundamental cerebellar computation is intact

The potential role of the cerebellum in the pathophysiology of dystonia has become a focus of recent research. However, direct evidence for a cerebellar contribution in humans with dystonia is difficult to obtain. We examined motor adaptation, a test of cerebellar function, in 20 subjects with primary cervical dystonia and an equal number of aged matched controls. Adaptation to both visuomotor (distorting visual feedback by 30°) and forcefield (applying a velocity-dependent force) conditions were tested. Our hypothesis was that cerebellar abnormalities observed in dystonia research would translate into deficits of cerebellar adaptation. We also examined the relationship between adaptation and dystonic head tremor as many primary tremor models implicate the cerebellothalamocortical network which is specifically tested by this motor paradigm. Rates of adaptation (learning) in cervical dystonia were identical to healthy controls in both visuomotor and forcefield tasks. Furthermore, the ability to adapt was not clearly related to clinical features of dystonic head tremor. We have shown that a key motor control function of the cerebellum is intact in the most common form of primary dystonia. These results have important implications for current anatomical models of the pathophysiology of dystonia. It is important to attempt to progress from general statements that implicate the cerebellum to a more specific evidence-based model. The role of the cerebellum in this enigmatic disease perhaps remains to be proven

Cerebellar learning distinguishes inflammatory neuropathy with and without tremor.

This study aims to investigate if patients with inflammatory neuropathies and tremor have evidence of dysfunction in the cerebellum and interactions in sensorimotor cortex compared to nontremulous patients and healthy controls

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

Facial tremor in dystonia.

Background: Tremor of the upper/middle part of the face, including the perinasal region and the forehead has been very rarely described in some patients with Parkinson's disease or Essential Tremor. It has not yet been reported in patients with idiopathic dystonia. Methods: We describe here a series of 8 patients with common forms of idiopathic focal/segmental dystonia with tremor involving the upper/middle part of the face, along with demonstrative videos and electrophysiological recordings. Results: The distribution of the tremor was confined to the face in two patients, whereas in six patients tremor was also evident either in the head/lower part of the face or in their upper limbs. Electrophysiological recordings disclosed a slightly irregular tremor with a frequency at about 3-5 Hz. Conclusions: A number of patients with classical forms of dystonia can show a tremor involving the upper/middle part of the face

Diagnosis of psychogenic tremor using a smartphone

Same embryo as in Confocal 2, centered more vegetally, and progressing further laterally. Shows that the entire vegetal endoderm is now internal, with the “vegetal” surface of the embryo being covered by cells that are much smaller than the initial vegetal endoderm cells, which can be seen inside the embryo. Confocal slices are 7 μm apart