Urinary extracellular vesicle dynamics in Parkinson's disease patients with urinary dysfunction.

Parkinson's disease (PD) presents with severe motor manifestations and a plethora of non-motor symptoms. Urinary dysfunctions are one of the most common non-motor symptoms of PD patients responsible for reduced quality of life. Urinary extracellular vesicles (EVs) are mostly considered to originate from the cells in the urogenital tract. In this study, we have performed urinary EV analysis in 29 PD cases with varied severity of urinary dysfunction and correlated it with the EV dynamics in 29 age-matched controls. In the studied cases, apart from urinary dysfunction, symptoms of depression, anxiety, cognitive dysfunction, sleep, and wakefulness were observed in >75% of the cases. No significant difference in urinary EV size, concentration and urinary EV protein concentration was observed between PD cases with urinary dysfunction and controls. However, a significant positive association was observed between urinary EV concentration and motor scores (p = 0.042), while no association was observed between urinary EV concentration and urinary dysfunction scores. Chronic stress induced by motor symptoms could be one of the reasons for excessive EV production in PD patients with urinary dysfunctions. Large-scale studies on the association of urinary EV dynamics with motor and non-motor symptoms may provide additional information on urinary dysfunction in PD.

Exome sequencing of choreoacanthocytosis reveals novel mutations in VPS13A and co-mutation in modifier gene(s).

Choreoacanthocytosis, one of the forms of neuroacanthocytosis, is caused by mutations in vacuolar protein sorting-associated protein A (VPS13A), and is often misdiagnosed with other form of neuroacanthocytosis with discrete genetic defects. The phenotypic variations among the patients with VPS13A mutations significantly obfuscates the understanding of the disease and treatment strategies. In this study, two unrelated cases were identified, exhibiting the core phenotype of neuroacanthocytosis but with considerable clinical heterogeneity. Case 1 presented with an additional Parkinsonism phenotype, whereas seizures were evident in case 2. To decipher the genetic basis, whole exome sequencing followed by validation with Sanger sequencing was performed. A known homozygous pathogenic nonsense mutation (c.799C > T; p.R267X) in exon 11 of the VPS13A gene was identified in case 1 that resulted in a truncated protein. A novel missense mutation (c.9263T > G; p.M3088R) in exon 69 of VPS13A identified in case 2 was predicted as pathogenic. In silico analysis of the p.M3088R mutation at the C-terminus of VPS13A suggests a loss of interaction with TOMM40 and may disrupt mitochondrial localization. We also observed an increase in mitochondrial DNA copy numbers in case 2. Mutation analysis revealed benign heterozygous variants in interacting partners of VPS13A such as VAPA in case 1. Our study confirmed the cases as ChAc and identified the novel homozygous variant of VPS13A (c.9263T > G; p.M3088R) within the mutation spectrum of VPS13A-associated ChAc. Furthermore, mutations in VPS13A and co-mutations in its potential interacting partner(s) might contribute to the diverse clinical manifestations of ChAc, which requires further study.

Improvement of "Bouncy Gait" in Lance-Adams Syndrome with Perampanel.

Lance-Adams syndrome (LAS) is chronic post-hypoxic myoclonus that is often associated with sudden lapses in muscle tone (negative myoclonus) in the legs, causing a disabling "bouncy gait." Given its relative rarity, there are no controlled treatment studies of LAS. The majority of cases require polypharmacy management, with an incomplete response. "Bouncy gait," in particular, is notoriously medication-refractory. Here, we report a patient with long-standing LAS who improved markedly when low-dose perampanel was added to his existing treatment regime consisting of clonazepam, levetiracetam, sodium valproate, and acetazolamide.

A clinical and electrophysiological study of peripheral neuropathies in peritoneal dialysis patients: Our experience from rural South India.

The objective was to study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in chronic kidney disease (CKD) patients on peritoneal dialysis (PD) and effect of the presence of diabetes mellitus (DM). Between May 2015 and December 2016, 100 CKD patients on PD were assessed. The prevalence of peripheral neuropathy was 65% based on clinical symptoms and 92% based on electrophysiological parameters. The mean age was 55.7 ± 10.9 years. About 64% were male. Twelve patients (12%) had motor weakness, 64 patients (64%) had positive symptoms and 60 patients (60%) had negative symptoms. Autonomic symptoms were seen in 14 patients (14%). Definite damage was seen in 68 patients (68%), early damage was seen in 16 patients (16%). In PD patients with DM (n = 50), 50 patients (100%) had definite damage. In PD patients without DM (n = 50), 18 patients (36%) had definite damage, 16 patients (32%) had early damage. In CKD patients on PD, patients aged >50 years (definite damage in 75.7%) showed more severe peripheral neuropathy when compared to patients aged ≤50 years (definite damage in 53%). Most common nerves involved in the present study were median motor nerve, sural nerve, ulnar sensory nerve, common peroneal nerve, posterior tibial nerve followed by the median sensory nerve. Peripheral neuropathy is common in CKD patients on PD, with higher prevalence and severity in elderly females and diabetics. Rationale management of diabetes in CKD patients on PD probably lowers the prevalence and severity of peripheral neuropathy.

Quality of Sleep and Sleep Disorders in Patients with Parkinsonism: A Polysomnography Based Study from Rural South India.

OBJECTIVE: The objective of this study is to study the quality of sleep, sleep disorders, and polysomnographic profile in Parkinsonism patients from rural areas and to correlate polysomnographic profile with the staging of disease and with sleep questionnaire. MATERIALS AND METHODS: Between May 2014 and December 2015, 168 Parkinsonism patients were prospectively screened using sleep questionnaire; Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Parkinson Disease Sleep Score-2 (PDSS-2). Sixty patients underwent overnight polysomnography subsequently. RESULTS: The mean age of 168 patients in the study was 65.3 ± 12.8 years. The mean duration of Parkinsonism was 4.6 ± 3.1 years. The mean ESS, PSQI and PDSS-2 were 12.4 ± 3.2, 7.9 ± 2.1 and 44.7 ± 5.8, respectively. A total of 148 patients (88.1%) had poor quality sleep, which was reported only in 37 patients (22%). Excessive daytime sleepiness (80%) and insomnia (76.7%) were most common symptoms. Polysomnographic profile showed poor sleep efficiency (median interquartile range [IQR] 74.8% [17.8%-99.5%]), reduced slow wave sleep (median [IQR] 0% [0%-9.5%]), and reduced rapid eye movement [REM] sleep (median (IQR) 4.9% [0.1%-24.2%]). Sleep disorders in the study were sleep fragmentation (n = 60, 100%), obstructive sleep apnea syndrome (n = 40, 66.7%), central sleep apnea syndrome (n = 6, 10%), and periodic limb movement disorder (n = 52, 86.7%). Two patients had REM sleep behavioral disorder clinically. There was statistically significant positive correlation between staging of disease, sleep latencies, and sleep questionnaire. CONCLUSION: Sleep is impaired in majority of Parkinsonism patients which needs to be diagnosed early and managed effectively. Patient education and awareness programs in rural areas regarding sleep disorders in Parkinsonism are required for early diagnosis.

A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis and Dialysis Patients: Our Experience from South India.

OBJECTIVE: To study the prevalence, clinical features, electrophysiological features and severity of peripheral neuropathy in chronic kidney disease (CKD) patients. METHODS: Between May 2015 and December 2016, 200 CKD patients and 25 controls were assessed prospectively. RESULTS: Prevalence of peripheral neuropathy in CKD patients was 50% based on clinical symptoms and 89% based on electrophysiological studies. Mean age of 200 CKD patients was 54.1 ± 11.9 years. 135 (67.5%) were male and 65 (32.5%) were female. Mean duration of disease was 4.2 ± 3.7 years. Positive sensory, negative sensory and autonomic symptoms were seen in 97(48.5%), 77(38.5%) and 17(8.5%) patients respectively. Symptomatic neuropathy was common in peritoneal dialysis patients. Definite and early damage was seen in 133 (66.5%) and 45 patients (22.5%) respectively, while 22 patients (11%) had no significant peripheral neuropathy. In predialysis patients (n=100); 63 (63%) had definite damage and 24(24%) had early damage. In peritoneal dialysis patients (n=50); 34(68%) had definite damage and 8(16%) had early damage. In hemodialysis patients (n=50); 36(72%) had definite damage and 13(26%) had early damage. Hemodialysis group (98%) showed more severe peripheral neuropathy. Most common nerves involved were sural, ulnar sensory, median sensory, common peroneal and posterioir tibial in CKD. Axonal and mixed sensorimotor neuropathy patterns were most common patterns in CKD. CONCLUSION: Peripheral neuropathy is common in CKD with highest prevalence and severity in hemodialysis group. Symptomatic peripheral neuropathy is common in peritoneal dialysis group. Newer treatment modalities are required to manage uremic neuropathy in early stage.

A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure.

OBJECTIVE: To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. MATERIALS AND METHODS: Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. RESULTS: The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure (n = 100) and severe renal failure patients (n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. CONCLUSION: Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics.

Kikuchi-Fujimoto disease presenting as brainstem encephalitis with secondary blepharospasm.

Central nervous system involvement in Kikuchi-Fujimoto disease is a very rare clinical manifestation. We report a 15-year-old girl who presented to us with fever, drowsiness, neck swellings, and involuntary closure of both eyelids of 2 days duration. Magnetic resonance imaging brain showed T2-weighted and fluid-attenuated inversion recovery hyperintensities in dorsal midbrain and pons. Cervical lymph node fine-needle aspiration cytology was suggestive of Kikuchi-Fujimoto disease. Blepharospasm secondary to infectious etiology is rare. Positron emission computed tomography brain showed increased focal uptake in anterior cingulate gyrus which can be the site of origin of blepharospasm. The patient was managed with steroids and trihexyphenidyl with significant recovery. Kikuchi-Fujimoto disease is a rare disease which has to be considered as one of the differential diagnosis in a case of acute encephalopathy with cervical lymphadenopathy.