Gastrointestinal Dysfunction in Parkinson’s Disease: Neuro-Gastroenterology Perspectives on a Multifaceted Problem

Patients with Parkinson’s disease (PD) face a multitude of gastrointestinal (GI) symptoms, including nausea, bloating, reduced bowel movements, and difficulties with defecation. These symptoms are common and may accumulate during the course of PD but are often under-recognized and challenging to manage. Objective testing can be burdensome to patients and does not correlate well with symptoms. Effective treatment options are limited. Evidence is often based on studies in the general population, and specific evidence in PD is scarce. Upper GI dysfunction may also interfere with the pharmacological treatment of PD motor symptoms, which poses significant management challenges. Several new less invasive assessment tools and novel treatment options have emerged in recent years. The current review provides an overview and a practical approach to recognizing and diagnosing common upper and lower GI problems in PD, e.g., dyspepsia, gastroparesis, small bowel dysfunction, chronic constipation, and defecatory dysfunction. Management aspects are discussed based on the latest evidence from the PD and general populations, with insights for future research pertaining to GI dysfunction in PD.

A KMT2B Frameshift Variant Causing Focal Dystonia Restricted to the Oromandibular Region After Long-Term Follow-up

KMT2B-linked dystonia (DYT-KMT2B) is a childhood-onset dystonia syndrome typically beginning in the lower limbs and progressing caudocranially to affect the upper limbs with eventual prominent craniocervical involvement. Despite its recent recognition, it now appears to be one of the more common monogenic causes of dystonia syndromes. Here, we present an atypical case of DYT-KMT2B with oromandibular dystonia as the presenting feature, which remained restricted to this region three decades after symptom onset. This appears to be the first reported case of DYT-KMT2B from Southeast Asia and provides further supporting evidence for the pathogenic impact of the KMT2B c.6210_6213delTGAG variant.

Fecal Calprotectin in Parkinson’s Disease and Multiple System Atrophy

Objective@#Converging evidence suggests that intestinal inflammation is involved in the pathogenesis of neurodegenerative diseases. Previous studies on fecal calprotectin in Parkinson’s disease (PD) were limited by small sample sizes, and literature regarding intestinal inflammation in multiple system atrophy (MSA) is very scarce. We investigated the levels of fecal calprotectin, a marker of intestinal inflammation, in PD and MSA. @*Methods@#We recruited 169 subjects (71 PD, 38 MSA, and 60 age-similar nonneurological controls). Clinico-demographic data were collected. PD and MSA were subtyped and the severity assessed using the MDS-UPDRS and UMSARS, respectively. Fecal calprotectin and blood immune markers were analyzed. @*Results@#Compared to controls (median: 35.7 [IQR: 114.2] μg/g), fecal calprotectin was significantly elevated in PD (median: 95.6 [IQR: 162.1] μg/g, p = 0.003) and even higher in MSA (median: 129.5 [IQR: 373.8] μg/g, p = 0.002). A significant interaction effect with age was observed; between-group differences were significant only in older subjects (i.e., ≥ 61 years) and became more apparent with increasing age. A total of 28.9% of MSA and 18.3% of PD patients had highly abnormal fecal calprotectin levels (≥ 250 μg/g); however, this difference was only significant for MSA compared to controls. Fecal calprotectin correlated moderately with selected blood immune markers in PD, but not with clinical features of PD or MSA. @*Conclusions@#Elevated fecal calprotectin suggests a role for intestinal inflammation in PD and MSA. A more complete understanding of gut immune alterations could open up new avenues of research and treatment for these debilitating diseases.

Hyperglycemia-Associated Hemichorea-Hemiballismus with Predominant Ipsilateral Putaminal Abnormality on Neuroimaging

No abstract available.

Alternating Hemiplegia of Childhood in a Person of Malay Ethnicity with Diffusion Tensor Imaging Abnormalities

No abstract available.

Chorea in Sporadic Creutzfeldt-Jakob Disease

No abstract available.

Purposeless Groaning in Parkinson's Disease

Purposeless groaning has been reported in advanced progressive supranuclear palsy. We present a case of purposeless groaning occurring as a primary complaint in a patient with advanced Parkinson's disease. Purposeless groaning is thought to be a manifestation of disinhibition and perseveration due to frontal-subcortical dysfunction. Proper recognition of this phenomenon will help clinicians to avoid unnecessary investigations and treatment (e.g., prescription of opioid medications).

A Patient with Beta-Propeller Protein-Associated Neurodegeneration: Treatment with Iron Chelation Therapy

We present a case of beta-propeller protein-associated neurodegeneration, a form of neurodegeneration with brain iron accumulation. The patient harbored a novel mutation in the WDR45 gene. A detailed video and description of her clinical condition are provided. Her movement disorder phenomenology was characterized primarily by limb stereotypies and gait dyspraxia. The patient's disability was advanced by the time iron-chelating therapy with deferiprone was initiated, and no clinical response in terms of cognitive function, behavior, speech, or movements were observed after one year of treatment.

Neurological melioidosis in East Malaysia: Case series and review of the literature

Melioidosis is an infectious disease caused by an aerobic, non-spore forming gram negative bacillus, Burkholderia pseudomallei. It is known to be of high incidence in parts of rural South East Asia, and in Northern Australia. Pneumonia is the commonest manifestation. We report here three cases of neurological melioidosis from the registry of 169 cases of melioidosis in Bintulu Hospital, Sarawak, East Malaysia, with a review of neurological melioidosis in the literature. The annual incidence of melioidosis is estimated to be 8 per 100,000 populations in the Bintulu district. Neurological melioidosis accounts for 1.8% of our melioidosis cases. A review of 76 cases of neurological melioidosis reported in the literature inclusive of our 3 cases shows that localized brain or spinal inflammation or abscess is the most common manifestation occurring in 80% of patients. Close to half (53%) have intra axial abscess (brain or spinal cord), a quarter (27%) have extra axial lesions only (epidural or subdural collection, osteomyelitis or scalp abscess), and another quarter (27%) have both intra and extra axial lesions. Thus, B. pseudomallei appears to be unique among the bacterial central nervous system infection to be able to affect the brain and its contiguous tissues, crossing the tissue plane particularly resulting in osteomyelitis, scalp abscess and vice versa. Two thirds of the neurologicalmelioidosis patients have only neurological disease with no evidence of disease elsewhere. Key words: Burkholderia pseudomallei; neurological melioidosis; Bintulu; Sarawak; Malaysia

The Association Between Bullous Pemphigoid and Neurological Disorders in A Selected Malaysian Population

Background: An association of bullous pemphigoid with neurological disorders has been reported. The objectives of this study were to review the clinical characteristics of patients with bullous pemphigoid and compare the association between bullous pemphigoid and various neurological disorders and comorbidities. Methods: This was a retrospective case-control study involving 43 patients with bullous pemphigoid and 43 age-, sex- and ethnicity-matched controls. Results: There was a statistically significant association between bullous pemphigoid and neurological disorders [Odds Ratio (OR) = 3.5, 95% Confidence Interval (CI) 1.3 to 9.2, p=0.011 and adjusted OR=3.5, 95% CI 1.2-10.3, p=0.026], in particular for dementia (p=0.002). Although stroke was more common among patients with bullous pemphigoid, this association was not statistically significant with OR of 1.9 (95% CI 0.7 to 5.2) and adjusted OR of 2.1 (95% CI 0.6 to 7.2). Similarly both ischaemic stroke (OR 1.5, 95% CI 0.5 to 4.2) and haemorrhagic stroke (OR 1.5, 95% CI 0.2 to 9.7) were more common. Other neurological disorders more common among patients with bullous pemphigoid were Parkinson’s disease and epilepsy. Dyslipidaemia was significantly less common among patients with bullous pemphigoid (OR 0.4, 95% CI 0.1 to 0.9, p=0.033). Conclusion: A combination of an inflammatory process, prothrombotic state and endothelial activation leads to an increased frequency of neurological disorders among patients with bullous pemphigoid. Thus, a holistic approach to patient care, including screening for dementia and control of comorbidities, should be practised as bullous pemphigoid affects more than just the skin.

Primary angiitis of the central nervous system with myelopathy as initial clinical presentation

Primary angiitis of the central nervous system (PACNS) is a rare vasculitis restricted to the central nervous system without systemic involvement. Delay in diagnosis and treatment is common due to its non-specific symptoms and lack of non-invasive diagnostic tests. Myelopathy can occur in PACNS, during the clinical course of the illness, with or without cerebral symptoms. We describe here a 51 year-old ethnic Chinese woman who presented initially with paraparesis without cerebral symptoms. The diagnosis of PACNS was eventually made from brain biopsy when she subsequently developed cerebral involvement. Despite aggressive treatment, the patient developed progressive neurological deterioration and died. This patient demonstrates the rare occurrence of myelopathy as the sole initial presentation of PACNS.

Lack of association between the LRRK2 A419V variant and Asian Parkinson's disease

<p><b>INTRODUCTION</b>The G2385R and R1628P LRRK2 gene variants have been associated with an increased risk of Parkinson's disease (PD) in the Asian population. Recently, a new LRRK2 gene variant, A419V, was reported to be a third risk variant for PD in Asian patients. Our objective was to investigate this finding in our cohort of Asian subjects.</p><p><b>MATERIALS AND METHODS</b>Eight hundred and twenty-eight subjects (404 PD patients, and 424 age and gender-matched control subjects without neurological disorders) were recruited. Genotyping was done by Taqman® allelic discrimination assay on an Applied Biosystems 7500 Fast Real-Time PCR machine.</p><p><b>RESULTS</b>The heterozygous A419V genotype was found in only 1 patient with PD, compared to 3 in the control group (0.4% vs 1.3%), giving an odds ratio of 0.35 (95% confidence interval (CI), 0.01 to 3.79; P = 0.624).</p><p><b>CONCLUSION</b>A419V is not an important LRRK2 risk variant in our Asian cohort of patients with PD. Our data are further supported by a literature review which showed that 4 out of 6 published studies reported a negative association of this variant in PD.</p>