A Pyramidal Cause of a Cerebellar Ataxia:HSP-7

A 43-year-old man presented with a slowly progressive fatigue and coordination problems, coupled with a radiological appearance of diffuse atrophy, especially in the cerebellar hemispheres. The diagnostic process was challenging because initially the additional investigations were focused on a cerebellar ataxia. In the following months, his ataxic gait developed in a more spastic pattern and whole exome sequencing revealed mutations in the SPG7 gene, confirming a diagnosis of hereditary spastic paraplegia. Therefore, the authors call for an extension of genetic panels in ataxia patients

Locked-In Syndrome after Traumatic Basilar Artery Entrapment within a Clivus Fracture:A Case Report and Review of the Literature

We report the case of a 58-year-old male with a rare vascular complication after traumatic head injury: entrapment of the basilar artery into a fracture of the clivus, ultimately leading to a locked-in syndrome due to brainstem infarction. Review of the literature revealed 19 earlier published cases of basilar artery entrapment within traumatic longitudinal clival fractures. In the majority of these patients there is an unfavorable neurological outcome

Supplementary Material for: A Pyramidal Cause of a Cerebellar Ataxia: HSP-7

A 43-year-old man presented with a slowly progressive fatigue and coordination problems, coupled with a radiological appearance of diffuse atrophy, especially in the cerebellar hemispheres. The diagnostic process was challenging because initially the additional investigations were focused on a cerebellar ataxia. In the following months, his ataxic gait developed in a more spastic pattern and whole exome sequencing revealed mutations in the SPG7 gene, confirming a diagnosis of hereditary spastic paraplegia. Therefore, the authors call for an extension of genetic panels in ataxia patients

Paroxismale kinesiogene dyskinesie

Paroxismale kinesiogene dyskinesie (PKD) is voor veel artsen een onbekende bewegingsstoornis, die zich kenmerkt door kortdurende episodes van abnormale bewegingen. Tussen deze aanvallen door is het neurologisch onderzoek bij patiënten met PKD in het geheel niet afwijkend. De diagnose is daardoor vaak lastig te stellen. Wij zien jaarlijks een behoorlijk aantal jonge patiënten met PKD bij wie deze aanvallen goed te behandelen zijn. Een filmpje van een aanval kan uitkomst bieden bij het stellen van de diagnose. Aan de hand van 2 patiënten en hun filmpjes laten wij zien dat er een aantal kenmerken zijn waardoor u de diagnose ‘PKD’ kunt stellen en uw patiënten direct kunt behandelen

Supplementary Material for: A Pyramidal Cause of a Cerebellar Ataxia: HSP-7

A 43-year-old man presented with a slowly progressive fatigue and coordination problems, coupled with a radiological appearance of diffuse atrophy, especially in the cerebellar hemispheres. The diagnostic process was challenging because initially the additional investigations were focused on a cerebellar ataxia. In the following months, his ataxic gait developed in a more spastic pattern and whole exome sequencing revealed mutations in the SPG7 gene, confirming a diagnosis of hereditary spastic paraplegia. Therefore, the authors call for an extension of genetic panels in ataxia patients

A novel diagnostic approach for patients with adult-onset dystonia

Adult-onset dystonia can be acquired, inherited or idiopathic. The dystonia is usually focal or segmental and for a limited number of cases causal treatment is available. In recent years, rapid developments in neuroimmunology have led to increased knowledge on autoantibody-related dystonias. At the same time, genetic diagnostics in sequencing technology have evolved and revealed several new genes associated with adult-onset dystonia. Furthermore, new phenotype-genotype correlations have been elucidated. Consequently, clinicians face the dilemma of which additional investigations should be performed and whether to perform genetic testing or not. To ensure early diagnosis and to prevent unnecessary investigations, integration of new diagnostic strategies is needed. We designed a new five-step diagnostic approach for adult-onset dystonia. The first four steps are based on a broad literature search and expert opinion, the fifth step, on when to perform genetic testing, is based on a detailed systematic literature review up to 1 December 2021. The basic principle of the algorithm is that genetic testing is unlikely to lead to changes in management in three groups: (1) patients with an acquired form of adult-onset dystonia; (2) patients with neurodegenerative disorders, presenting with a combined movement disorder including dystonic symptoms and (3) patients with adult-onset isolated focal or segmental dystonia. Throughout the approach, focus lies on early identification of treatable forms of dystonia, either acquired or genetic. This novel diagnostic approach for adult-onset dystonia can help clinicians to decide when to perform additional tests, including genetic testing and facilitates early aetiological diagnosis, to enable timely treatment

A Critical Appraisal of the Whack-a-Mole and Swivel Chair Signs in the Diagnosis of Functional Movement Disorders

Background: The demonstration of positive signs during neurological examination is a cornerstone of the diagnosis of functional movement disorders, however, the available data supporting the diagnostic value of some of these signs is limited. Objectives: To determine the diagnostic value (sensitivity and specificity) of the “whack-a-mole” (WAM) and “swivel chair” (SC) tests in patients with functional movement disorders (FMD). Methods: We enrolled patients with functional and organic movements in the WAM test if they exhibited tremor, dystonia, myoclonus, chorea, or tics. For the SC test, patients with a gait disorder as their primary impairment were recruited. Two blinded movement disorder specialists rated the presence of these signs in edited videos. Results: Inclusion criteria were met by 42 patients with FMD and 65 patients with organic movement disorders. Both tests demonstrated high specificity (means, 78% and 96%), but their sensitivity was low (means, 52% and 37%). Interobserver agreement for the WAM sign was 0.77 in the FMD group, against 0.28 in patients with organic movement disorders, whereas Movement Disorders Clinical Practice for Review Only for the SC sign was 0.69 in both groups. Conclusions: The present study indicates that physicians must be cautious in the application and interpretation of these clinical signs in the diagnosis of functional movement disorders, and they should be carefully considered and used as necessary.</p

Rare functional missense variants in CACNA1H: What can we learn from Writer's cramp?

Writer's cramp (WC) is a task-specific focal dystonia that occurs selectively in the hand and arm during writing. Previous studies have shown a role for genetics in the pathology of task-specific focal dystonia. However, to date, no causal gene has been reported for task-specific focal dystonia, including WC. In this study, we investigated the genetic background of a large Dutch family with autosomal dominant‒inherited WC that was negative for mutations in known dystonia genes. Whole exome sequencing identified 4 rare variants of unknown significance that segregated in the family. One candidate gene was selected for follow-up, Calcium Voltage-Gated Channel Subunit Alpha1 H, CACNA1H, due to its links with the known dystonia gene Potassium Channel Tetramerization Domain Containing 17, KCTD17, and with paroxysmal movement disorders. Targeted resequencing of CACNA1H in 82 WC cases identified another rare, putative damaging variant in a familial WC case that did not segregate. Using structural modelling and functional studies in vitro, we show that both the segregating p.Arg481Cys variant and the non-segregating p.Glu1881Lys variant very likely cause structural changes to the Cav3.2 protein and lead to similar gains of function, as seen in an accelerated recovery from inactivation. Both mutant channels are thus available for re-activation earlier, which may lead to an increase in intracellular calcium and increased neuronal excitability. Overall, we conclude that rare functional variants in CACNA1H need to be interpreted very carefully, and additional studies are needed to prove that the p.Arg481Cys variant is the cause of WC in the large Dutch family