Elizabeth Slow

C9orf72 and ATXN2 repeat expansions coexist in a family with ataxia, dementia, and parkinsonism.

Intermediate interrupted ataxin 2 (ATXN2) alleles (27–33 CAG‐repeats) increase the risk for amyotrophic lateral sclerosis and are reported as modifiers in chromosome 9 open reading frame 72 (C9orf72) carriers, rendering susceptibility to amyotrophic lateral sclerosis rather than frontotemporal lobar degeneration. The clinical presentation of C9orf72 patients with pathogenic ATXN2 alleles (≥35 CAG‐repeats) is unknown.

Deep brain stimulation for treatment of dystonia secondary to stroke or trauma

Globus pallidus pars interna (GPi) deep brain stimulation (DBS) is efficacious for reduction of medically refractory, primary, generalised dystonia and subtypes of acquired dystonia,1 but there is little evidence supporting the efficacy of DBS in dystonia acquired after stroke or traumatic brain injury (TBI). Dystonia has been reported in up to 4% of patients with post-stroke2 and up to 20% of patients after severe TBI.3 Patients who develop dystonia after stroke or TBI are typically adolescents/young adults, in whom dystonia manifests in days to years after the initial event. Brain MRI abnormalities are often present, typically in the basal ganglia. The most frequent type of dystonia observed in this population is hemidystonia, which is usually refractory to medical management.3 Since young adults are predominantly afflicted and the dystonia is often medically refractory, this population experiences significant disability for the majority of their lifetime. In order to determine if DBS can be beneficial to this population, we have analysed patients’ outcomes from the Toronto Western Hospital (TWH) DBS database in a retrospective, observational study. All patients who received DBS for dystonia acquired after stroke/TBI were identified through a search of the TWH DBS dystonia database (1995–2012) and were included in the study. Dystonia was diagnosed by a movement disorder neurologist. The study was reviewed and approved by the Research Ethics Board of the University Health Network. Details of DBS surgery have been published previously.4 Post-DBS MRI were performed to verify correct …

Oculogyric crises: A review of phenomenology, etiology, pathogenesis, and treatment

Oculogyric crises are a rare movement disorder characterized by paroxysmal, conjugate, tonic, usually upwards, deviation of the eyes. Causes for oculogyric crises are limited and include complications of dopamine‐receptor blocking medications and neurometabolic disorders affecting dopamine metabolism, suggesting that an underlying hypodopaminergic state is important to the pathogenesis. Mimickers of oculogyric crises exist, and we propose diagnostic criteria to distinguish true oculogyric crises. Recognition of oculogyric crises is important for the diagnosis and appropriate treatment of rare disorders, and an approach to investigations in oculogyric crises is proposed.

Heart rate variability in leucine-rich repeat kinase 2-associated Parkinson's disease

Heart rate variability is reduced in idiopathic PD, indicating cardiac autonomic dysfunction likely resulting from peripheral autonomic synucleinopathy. Little is known about heart rate variability in leucine‐rich repeat kinase 2‐associated PD.

Movement disorder society criteria for clinically established early Parkinson's disease: Clinically Established Early PD Criteria

Background: In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinsons disease (PD). Although recent validation studies suggest high accuracy, one unmet need is for highly specific criteria for clinical trials in early/de novo PD.

Dystonic Pseudo Foot Drop

The most common presentation of foot dystonia in patients with Parkinsons disease (PD) or dystonia is inversion of the foot accompanied by flexion of the toes, with or without extension of the hallux. Less commonly, foot dystonia may mimic foot drop, as occurs with weakness of the dorsiflexors muscles, resulting in a pseudo foot drop. This has rarely been reported in the literature and has been poorly recognized, often leading to misdiagnosis and unnecessary investigations and treatment. We report 5 patients with dystonic pseudo foot drop, one of them diagnosed with early‐onset PD, 2 with sporadic PD, and 2 with dystonia. Despite the steppage gait, their physical exam revealed normal strength, and no other explanation for a “foot drop” was found. It is important to recognize this phenomenology, which can be a clue to the diagnosis of early‐onset PD, and may be responsive to levodopa in selected patients.

ADCK3-related Coenzyme Q10 Deficiency: A Potentially Treatable Genetic Disease: Expanding Phenotype of Coenzyme Q10 Deficiency

Disorders related to dysfunction of coenzyme (CoQ10) metabolism, including AarF domain containing kinase 3 gene (ADCK3) mutations, have received attention due to the potential for response to CoQ10 supplementation.

CLIPPERS: A Treatable Cause of Spastic Ataxia: CLIPPERS Causing Spastic Ataxia

A 28 year-old man was first seen in our clinic in September 2016. At the age of 18, he first noticed mild balance difficulties when running down stairs. After moving home at age 22, it became more obvious that his walking was abnormal and his family physician detected stiffness in his legs. He was referred to a neurologist who embarked on neurological investigations. This led to an initial diagnosis of multiple sclerosis, which was later retracted. Over the next few years, he was started on antispasticity medications and his condition was stable. However, by the age of 26, he felt too unsteady to walk the dog and began falling. His parents observed that he had a tendency to laugh at inappropriate times (e.g., when attending a funeral). He described intermittent diplopia and the sensation of a “tight swimming cap” around his scalp. There was no family history of neurological problems. Examination revealed spastic ataxia with pseudobulbar affect (Video S1). Magnetic resonance (MR) brain scan in 2012 revealed white matter FLAIR hyperintensities (Fig. S1) with corresponding enhancement on post-gadolinium sequences involving the pons, deep cerebellar, and supratentorial periventricular white matter that followed a perivascular distribution (Fig. 1). Follow-up imaging in 2017 (prior to any treatment) demonstrated a spontaneously fluctuating evolution of the perivascular enhancement, with some new foci and some regressed foci (Fig. 1). There was moderate bilateral cerebellar atrophy. Previous cerebrospinal fluid analysis revealed mildly raised white cell count (11 x 10/L, 100% lymphocytes) and protein (0.54 g/L), but no other abnormalities (including oligoclonal bands, cytology, and flow cytometry). Other past investigations were normal or negative (Text S1). Clinical and radiological features fulfilled diagnostic criteria for “probable chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS)”. We administered intravenous methylprednisolone 1g once daily for five days, followed by oral prednisolone 60 mg once daily for three months. Eight weeks later, repeat MR brain scan revealed complete resolution of the lesional enhancement (Fig. 1), with the FLAIR hyperintensity burden largely unchanged (Fig. S1). His walking was slightly better (his parents noticed that he was dragging his legs less) and the sensory disturbance affecting his scalp improved by 50%. He still had considerable residual disability (requiring a cane to walk even short distances outside), reflecting the damage accumulated over the years. We plan to start him on mycophenolate mofetil as a steroid-sparing agent. In 2010, CLIPPERS was first described in eight patients (aged 16–86 years) presenting with subacute gait ataxia and diplopia. Similar to our case, dysarthria, altered sensation of the scalp, pseudobulbar affect and spasticity were observed in some cases. Other movement disorder presentations are recognised including Holmes tremor, dystonia, jerks secondary to epilepsia partialis continua, and irregular palatal movements. The original case series recognized that the radiological hallmark of CLIPPERS was punctate and curvilinear enhancement peppering the pons and extending variably into other parts of the brainstem. More subtle enhancing lesions were described in the basal ganglia, cerebellar white matter, corpus callosum, and spinal cord. Supratentorial lesions have since been described. Spinal fluid is sometimes abnormal (e.g., mildly raised protein, mild lymphocytic pleocytosis and/or unmatched oligoclonal bands). Brain biopsy shows predominantly white matter-based perivascular and parenchymal lymphocytic infiltrate (mainly T lymphocytes) without demyelination, granulomatous inflammatory, or necrotising vasculitic pattern. At present, the aetiology of CLIPPERS is unknown. Steroid treatment is successful in improving clinical and radiological disease, but complete recovery is uncommon (especially if treatment is delayed as was the case in our patient). The optimal long-term immunosuppressive strategy has not been established.

Clustering of motor and nonmotor traits in leucine-rich repeat kinase 2 G2019S Parkinson's disease nonparkinsonian relatives: A multicenter family study: SHARED TRAITS IN NONPARKINSONIAN RELATIVES OF LRRK2 G2019S PD

The objective of this study was to determine phenotypic features that differentiate nonparkinsonian first‐degree relatives of PD leucine‐rich repeat kinase 2 (LRRK2) G2019S multiplex families, regardless of carrier status, from healthy controls because nonparkinsonian individuals in multiplex families seem to share a propensity to present neurological features.

Validation of the MDS clinical diagnostic criteria for Parkinson's disease: Validation of MDS Criteria

Background: In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinsons disease. These criteria aimed to codify/reproduce the expert clinical diagnostic process and to help standardize diagnosis in research and clinical settings. Their accuracy compared with expert clinical diagnosis has not been tested. The objectives of this study were to validate the International Parkinson and Movement Disorder Society diagnostic criteria against a gold standard of expert clinical diagnosis, and to compare concordance/accuracy of the International Parkinson and Movement Disorder Society criteria to 1988 United Kingdom Brain Bank criteria.