Adult-Onset Isolated Hemichorea Revealing Iatrogenic Hypoparathyroidism and Bilateral Basal Ganglia Calcification.

Isolated hemichorea (HC) in adults has a relatively restricted differential diagnosis including stroke of contralateral basal ganglia nuclei, nonketotic hyperglycemia, and basal ganglia toxoplasmosis in HIV infection. Hypoparathyroidism-related basal ganglia calcification can potentially cause neurological problems, including movement disorders, that are usually bilateral in keeping with bilateral symmetric lesions. We report a patient with video-documented isolated, adult-onset HC due to iatrogenic hypoparathyroidism and bilateral basal ganglia calcification. A 47-year-old woman presented with isolated adult-onset HC of 2 years' duration as the presenting and only neurological feature of hypoparathyroidism and bilateral extensive basal ganglia calcification, 20 years after thyroidectomy-induced hypoparathyroidism. Significant improvement in the unilateral hyperkinesia was noted after correction of hypocalcemia and hypoparathyroidism at 3 months. Isolated HC in adults is a rare presenting feature of hypoparathyroidism with bilateral basal ganglia calcification and is treatable with correction of the underlying metabolic abnormality. In all cases with a movement disorder and brain calcification, hypoparathyroidism should be actively sought as this treatable condition must not be missed.

Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies.

BACKGROUND: People with Parkinson's disease can show premotor neurochemical changes in the dopaminergic and non-dopaminergic systems. Using PET, we assessed whether dopaminergic and serotonin transporter changes are similar in LRRK2 mutation carriers with Parkinson's disease and individuals with sporadic Parkinson's disease, and whether LRRK2 mutation carriers without motor symptoms show PET changes. METHODS: We did two cross-sectional PET studies at the Pacific Parkinson's Research Centre in Vancouver, BC, Canada. We included LRRK2 mutation carriers with or without manifest Parkinson's disease, people with sporadic Parkinson's disease, and age-matched healthy controls, all aged 18 years or older. People with Parkinson's disease were diagnosed by a neurologist with movement disorder training, in accordance with the UK Parkinson's Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger sequencing. In the first study, LRRK2 mutation carriers with or without manifest Parkinson's disease who were referred for investigation between July, 1999, and January, 2012, were scanned with PET tracers for the membrane dopamine transporter, and dopamine synthesis and storage (18F-6-fluoro-L-dopa; 18F-FDOPA). We compared findings with those in people with sporadic Parkinson's disease and age-matched healthy controls. In the second study, distinct groups of LRRK2 mutation carriers, individuals with sporadic Parkinson's disease, and age-matched healthy controls seen from November, 2012, to May, 2016, were studied with tracers for the serotonin transporter and vesicular monoamine transporter 2 (VMAT2). Striatal dopamine transporter binding, VMAT2 binding, 18F-FDOPA uptake, and serotonin transporter binding in multiple brain regions were compared by ANCOVA, adjusted for age. FINDINGS: Between January, 1997, and January, 2012, we obtained data for our first study from 40 LRRK2 mutation carriers, 63 individuals with sporadic Parkinson's disease, and 35 healthy controls. We identified significant group differences in striatal dopamine transporter binding (all age ranges in caudate and putamen, p<0·0001) and 18F-FDOPA uptake (in caudate: age ≤50 years, p=0·0002; all other age ranges, p<0·0001; in putamen: all age ranges, p<0·0001). LRRK2 mutation carriers with manifest Parkinson's disease (n=15) had reduced striatal dopamine transporter binding and 18F-FDOPA uptake, comparable with amounts seen in individuals with sporadic Parkinson's disease of similar duration. LRRK2 mutation carriers without manifest Parkinson's disease (n=25) had greater 18F-FDOPA uptake and dopamine transporter binding than did individuals with sporadic Parkinson's disease, with 18F-FDOPA uptake comparable with controls and dopamine transporter binding lower than in controls. Between November, 2012, and May, 2016, we obtained data for our second study from 16 LRRK2 mutation carriers, 13 individuals with sporadic Parkinson's disease, and nine healthy controls. Nine LRRK2 mutation carriers without manifest Parkinson's disease had significantly elevated serotonin transporter binding in the hypothalamus (compared with controls, individuals with LRRK2 Parkinson's disease, and people with sporadic Parkinson's disease, p<0·0001), striatum (compared with people with sporadic Parkinson's disease, p=0·02), and brainstem (compared with LRRK2 mutation carriers with manifest Parkinson's disease, p=0·01), after adjustment for age. Serotonin transporter binding in the cortex did not differ significantly between groups after age adjustment. Striatal VMAT2 binding was reduced in all individuals with manifest Parkinson's disease and reduced asymmetrically in one LRRK2 mutation carrier without manifest disease. INTERPRETATION: Dopaminergic and serotonergic changes progress in a similar fashion in LRRK2 mutation carriers with manifest Parkinson's disease and individuals with sporadic Parkinson's disease, but LRRK2 mutation carriers without manifest Parkinson's disease show increased serotonin transporter binding in the striatum, brainstem, and hypothalamus, possibly reflecting compensatory changes in serotonergic innervation preceding the motor onset of Parkinson's disease. Increased serotonergic innervation might contribute to clinical differences in LRRK2 Parkinson's disease, including the emergence of non-motor symptoms and, potentially, differences in the long-term response to levodopa. FUNDING: Canada Research Chairs, Michael J Fox Foundation, National Institutes of Health, Pacific Alzheimer Research Foundation, Pacific Parkinson's Research Institute, National Research Council of Canada.

In vivo dopaminergic and serotonergic dysfunction in DCTN1 gene mutation carriers.

INTRODUCTION: We used positron emission tomography (PET) to assess dopaminergic and serotonergic terminal density in three subjects carrying a mutation in the DCT1 gene, two clinically affected with Perry syndrome. METHODS: All subjects had brain imaging using 18F-6-fluoro-l-dopa (FDOPA, dopamine synthesis and storage), (+)-11C-dihydrotetrabenazine (DTBZ, vesicular monoamine transporter type 2), and 11C-raclopride (RAC, dopamine D2/D3 receptors). One subject also underwent PET with 11C-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB, serotonin transporter). RESULTS: FDOPA-PET and DTBZ-PET in the affected individuals showed a reduction of striatal tracer uptake. Also, RAC-PET showed higher uptake in these area. DASB-PET showed significant uptake changes in left orbitofrontal cortex, bilateral anterior insula, left dorsolateral prefrontal cortex, left orbitofrontal cortex, left posterior cingulate cortex, left caudate, and left ventral striatum. CONCLUSIONS: Our data showed evidence of both striatal dopaminergic and widespread cortical/subcortical serotonergic dysfunctions in individuals carrying a mutation in the DCTN1 gene.

Biomarkers for trials of neuroprotection in Parkinson's disease.

With increased understanding of disease pathogenesis and the foreseeable reality of disease-modifying therapies, there is a growing need to find biomarkers that will allow early (preferably preclinical) detection of disease and that will provide an independent readout of disease progression. In this article, we review a variety of markers, with a focus on functional imaging techniques, which while imperfect, currently provide the best approach to this problem. We consider the limitations of functional imaging of the dopamine system in assessing the progression of Parkinson's Disease (PD) as well as the potential use of structural imaging and emerging progress in other biochemical and molecular markers. While there is no single biomarker that will satisfy all requirements, some combination is likely to be of great use in identifying those subjects most likely to benefit from neuroprotective therapies, as well as in monitoring the effects of these interventions.

Glutamic acid decarboxylase antibody-positive paraneoplastic stiff limb syndrome associated with carcinoma of the breast.

Stiff limb syndrome (SLS) is a rare "focal" variant of stiff person syndrome which presents with rigidity and painful spasms of a distal limb, and abnormal fixed foot or hand postures. Anti-glutamic acid decarboxylase antibodies (GAD-Ab) are variably present in most cases. Most reported cases of SLS are unassociated with cancer. We describe a patient with SLS as a paraneoplastic manifestation of breast carcinoma, in whom GAD-Ab was present. The patient responded very well to oral diazepam, baclofen and steroids.This is the third reported case of SLS as a paraneoplastic accompaniment to cancer.

Primary central nervous system lymphoma: a profile of 26 cases from Western India.

BACKGROUND: Primary central nervous system (CNS) lymphoma (PCNSL) is a rare malignant non-Hodgkin's lymphoma and it accounts for 1% of all intracranial tumors. Only a few PCNSL studies have been reported from India, and studies on prognostic factors determining outcome, or evaluation of the response to currently accepted treatment, are lacking. AIMS: This study attempts to further delineate the clinical, radiological and pathological profile of PCNSL in India, to evaluate response to treatment and to assess usefulness of the International Extranodal Lymphoma Study Group (IELSG) score. SETTINGS AND DESIGN: All patients with pathologically proven PCNSL admitted over three years at a large tertiary care institution were studied. MATERIALS AND METHODS: Clinical features, IELSG prognostic score, imaging and pathological features, and response to treatment were evaluated. Results were analyzed using chi 2 test. RESULTS: Of 26 patients found, all except two were immunocompetent. Median age at diagnosis was 59 years. Focal deficits (76.9%) and neuropsychiatric symptoms (57.6%) were the commonest presenting complaints. Except for one case, at least some contrast enhancement was seen in brain lesions of all patients. Pathological studies showed high grade diffuse large B-cell (DLBCL) histology in 96.2% of patients. Of 22 patients who received methotrexate (MTX) based chemotherapy with/without radiotherapy; six died, with a response rate of 72.7%. Median survival was 10 months. Median follow-up duration was 14.5 months. Four patients developed treatment-related cognitive decline. All six patients with IELSG score of 4/5 died, while all 16 patients with a score of 0-3 survived. CONCLUSIONS: PCNSL presents most commonly in the sixth decade with focal neurological deficit, behavioral symptoms and cognitive decline. High grade DLBCL is the commonest histological subtype. Steroids should ideally be withheld until biopsy as they may confound the diagnosis. Most immunocompetent patients respond well to high dose MTX-based chemotherapy with/without radiation. High IELSG scores correlate with worse prognosis in patients with PCNSL.

Dermoid of the conus medullaris.

Dermoids are rare midline tumours. When involving the spinal cord they usually present early, in the first decade of life. We present a case of an elderly male with paraparesis. His MRI showed cord expansion at the tip of the conus medullaris; contrast enhancement with Gadolinium revealed a cystic lesion and histopathology confirmed the diagnosis of a dermoid cyst.

Neurofibromatosis type I presenting with urinary retention and lung collapse.

A 26-year-old male presented with urinary retention, spastic paraparesis and a swelling in the right side of the neck. Urinary retention was due to a neurofibroma of a lumbar spinal root compressing the urinary bladder and right ureter retroperitoneally. Paraparesis was due to an intraspinal neurofibroma causing cord compression at the cervicodorsal junction. In addition, this tumour was contiguous with the mass in the neck, and also with another large mass in the right hemithorax which was causing collapse of the right lung.