Levodopa-Carbidopa Intestinal Gel for Parkinson's Disease over 11 years: One Center's "Real-World" Experience.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) therapy has been shown to be a safe and effective treatment for advanced Parkinson's disease (PD). Limited data are available regarding long-term benefits and complications in Canada. Objective of the study was to review long-term experience and clinical outcomes in PD patients with LCIG therapy over 11 years in a multidisciplinary University clinic setting. METHODS: Chart review was done on PD patients with LCIG from 2011 to 2022. Data collected: dosing, UPDRS-III motor scores, OFF times, hours with dyskinesias, MoCA, complications, discontinuation reasons, and nursing time requirements. RESULTS: Thirty-three patients received LCIG therapy with a mean follow-up of 3.25±2.09 years. UPDRS-III scores showed reduction of 15% from baseline (mean 35.9) up to 4 years (mean 30.4). Daily OFF time improved from baseline (mean 7.1 ± 3.13 hours) up to 5 years (mean 3.3 ± 2.31 hours; -53.5%; p < 0.048), and dyskinesias remained stable. Nursing time averaged 22 hours per patient per year after PEG-J insertion and titration. Most common complications were PEG-J tube dislodgement and stoma site infection (0-3zero to three events/patient/year). Serious side effects were seen in four (12%) patients resulting in hospitalization and/or death. Nine patients (27.2%) discontinued the treatment due to lack of improved efficacy over oral therapy or development of dementia and 10 (30%) died of causes unrelated to LCIG infusion. CONCLUSION: Patients on LCIG showed improved motor function over 5-year follow-up. Serious complications were uncommon. Dedicated nursing time is required by LCIG-trained nurses in a multidisciplinary setting for optimum management.

A Cross-sectional Study of Cardiovascular Involvement in Systemic Lupus Erythematosus in an Urban Indian Tertiary Care Centre with Emphasis on 2-D Echocardiography.

BACKGROUND: Cardiovascular manifestations are responsible for considerable morbidity and mortality in patients with SLE. A wide range of manifestations due to active lupus, like pericarditis, valvular affection, myocarditis, and less commonly pulmonary hypertension, are described. This study was undertaken to study cardiovascular manifestations in SLE, with a focus on echocardiography findings, in an urban Indian setting. METHODOLOGY: Fifty consecutive cases of SLE following up in the Rheumatology Clinic of TNMC and BYL Nair Charitable hospital, an Indian tertiary care hospital were studied. They were subjected to an echocardiographic examination if not already done. Detailed history, examination, study of past medical records and investigations were carried out, especially related to cardiovascular system. Treatment details, flares, other systemic involvement were noted. Serial echocardiography if done previously were noted down. The data was analysed using descriptive statistics. RESULTS: An echocardiographic abnormality was noted in 25 (50%) of the 50 subjects. Pulmonary hypertension in 21(42%); valvular abnormalities in 16 (32 %); pericardial effusion in 9 (18%) and diastolic dysfunction in 6(12%) were the echocardiography findings. Six out of the 7 cases with moderately to severe pulmonary hypertension seemed to be responding to immunosuppressive therapy clinically as well as on echocardiography; 1 did not respond. At least 1 traditional risk factor for atherosclerosis was present in 58% of cases. CONCLUSIONS: Screening echocardiography may be recommended, especially at presentation, during SLE flare, or in the presence of cardiac symptoms. Moderate to severe pulmonary hypertension can develop any time in the course of the disease. It may be responsive to immunosuppression. Further detailed studies including multiple echocardiographic parameters and right heart catheterisation need to be undertaken to study the responsiveness of pulmonary hypertension to immunosuppresssive therapy.

Trends in Stroke Presentations before and during the COVID-19 Pandemic: A Meta-Analysis.

BACKGROUND AND PURPOSE: There are reports of decline in the rates of acute emergency presentations during coronavirus disease 2019 (COVID-19) pandemic including stroke. We performed a meta-analysis of the impact of COVID-19 pandemic on rates of stroke presentations and on rates of reperfusion therapy. METHODS: Following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines, we systematically searched the literature for studies reporting changes in stroke presentations and treatment rates before and during the COVID-19 pandemic. Aggregated data were pooled using meta-analysis with random-effect models. RESULTS: We identified 37 observational studies (n=375,657). Pooled analysis showed decline in rates of all strokes (26.0%; 95% confidence interval [CI], 22.4 to 29.7) and its subtypes; ischemic (25.3%; 95% CI, 21.0 to 30.0), hemorrhagic (27.6%; 95% CI, 20.4 to 35.5), transient ischemic attacks (41.9%; 95% CI, 34.8 to 49.3), and stroke mimics (45.6%; 95% CI, 33.5 to 58.0) during months of pandemic compared with the pre-pandemic period. The decline was most evident for mild symptoms (40% mild vs. 25%-29% moderate/severe). Although rates of intravenous thrombolytic (IVT) and endovascular thrombectomy (EVT) decreased during pandemic, the likelihood of being treated with IVT and EVT did not differ between the two periods, both in primary and in comprehensive stroke centers (odds ratio [OR], 1.08; 95% CI, 0.94 to 1.24 and OR, 0.95; 95% CI, 0.83 to 1.09, respectively). CONCLUSIONS: Rates of all strokes types decreased significantly during pandemic. It is of paramount importance that general population should be educated to seek medical care immediately for stroke-like symptoms during COVID-19 pandemic. Whether delay in initiation of secondary prevention would affect eventual stroke outcomes in the long run needs further study.

Mitochondrial leukoencephalopathies: A border zone between acquired and inherited white matter disorders in children?

BACKGROUND: There is emerging evidence implicating mitochondrial dysfunction in the pathogenesis of acquired demyelinating disorders such as multiple sclerosis. On the other hand, some of the primary mitochondrial disorders such as mitochondrial leukoencephalopathies exhibit evidence of neuroinflammation on MRI. The inter-relationship between mitochondrial disorders and episodic CNS inflammation needs exploration because of the therapeutic implications. OBJECTIVE: We sought to analyze the clinical course and MRI characteristics in a cohort of patients with mitochondrial leukoencephalopathy to determine features, if any, that mimic primary demyelinating disorders. Therapeutic implications of these findings are discussed. PATIENTS AND METHODS: Detailed analysis of the clinical course, magnetic resonance imaging findings and therapeutic response was performed in 14 patients with mitochondrial leukoencephalopathy. The diagnosis was ascertained by clinical features, histopathology, respiratory chain enzyme assays and exome sequencing. RESULTS: Fourteen patients [Age at evaluation: 2-7 yrs, M: F-1:1] were included in the study. The genetic findings included variations in NDUFA1 (1); NDUFV1 (4); NDUFS2 (2); LYRM (2);MPV17(1); BOLA3(2); IBA57(2). Clinical Features which mimicked acquired demyelinating disorder included acute onset focal deficits associated with encephalopathy [10/14, 71%], febrile illness preceding the onset [7/14, 50%] unequivocal partial or complete steroid responsiveness [11/11], episodic/ relapsing remitting neurological dysfunction [10/14, 71%] and a subsequent stable rather than a progressive course [12/14, 85%]. MRI characteristics included confluent white matter lesions [14/14, 100%], diffusion restriction [11/14,78.5%], contrast enhancement [13/13,100%], spinal cord involvement [8/13,61.5%], lactate peak on MRS [13/13] and white matter cysts [13/14, 92.8%]. CONCLUSION: Clinical presentations of mitochondrial leukoencephalopathy often mimic an acquired demyelinating disorder. The therapeutic implications of these observations require further exploration.

Outcome of epilepsy in patients with mitochondrial disorders: Phenotype genotype and magnetic resonance imaging correlations.

OBJECTIVES: Studies exploring the outcome of epilepsy in patients with mitochondrial disorders are limited. This study examined the outcome of epilepsy in patients with mitochondrial disorders and its relation with the clinical phenotype, genotype and magnetic resonance imaging findings. PATIENTS AND METHODS: The cohort was derived from the database of 67 patients with definite genetic diagnosis of mitochondrial disorders evaluated over a period of 11years (2006-2016). Among this, 27 had epilepsy and were included in final analysis. Data were analyzed with special reference to clinical phenotypes, genotypes, epilepsy characteristics, EEG findings, anti epileptic drugs used, therapeutic response, and magnetic resonance imaging findings. Patients were divided into three groups according to the seizure frequency at the time of last follow up: Group I- Seizure free; Group II- Infrequent seizures; Group III- uncontrolled seizures. For each group the clinical phenotype, genotype, magnetic resonance imaging and duration of epilepsy were compared. RESULTS: The phenotypes & genotypes included Mitochondrial Encephalopathy Lactic Acidosis and Stroke like episodes (MELAS) & m.3243A>G mutation (n = 10), Myoclonic Epilepsy Ragged Red Fiber syndrome (MERRF) & m.8344A>G mutation (n = 4), Chronic Progressive External Ophthalmoplegia plus &POLG1 mutation (CPEO, n = 6), episodic neuroregression due to nuclear mutations (n = 6; NDUFV1 (n = 3), NDUFA1, NDUFS2, MPV17-1 one each), and one patient with infantile basal ganglia stroke syndrome, mineralizing angiopathy &MT-ND5 mutations. Seven patients (25.9%) were seizure free; seven had infrequent seizures (25.9%), while thirteen (48.1%) had frequent uncontrolled seizures. Majority of the subjects in seizure free group had episodic neuroregression & leukoencephalopathy due to nuclear mutations (85.7%). Patients in group II with infrequent seizures had CPEO, POLG1 mutation and a normal MRI (71%) while 62% of the subjects in group III had MELAS, m.3243A>G mutation and stroke like lesions on MRI. CONCLUSIONS: A fair correlation exists between the outcome of epilepsy, clinical phenotypes, genotypes and magnetic resonance imaging findings in patients with mitochondrial disorders. The recognition of these patterns is important clinically because of the therapeutic and prognostic implications.

Sporadic Hyperekplexia Plus Syndrome.

A disorder of infants and children with pathological startle response, features of other system involvement, falls, and stiffness with retained consciousness. It should be differentiated from conditions such as myoclonic epilepsy, psychogenic movement disorder, Isaac syndrome, Schwartz-Jampel syndrome, Gilles de la Tourette, and culture-specific startle syndromes such as jumping Frenchman of Maine. A 5-year-old child symptomatic with repeated falls spontaneously as well as by sound and activities since neonatal period. He was having hyperalert facies, intelligent, cooperative with mild dysmorphism. His investigations were noncontributory except giant somatosensory evoked potentials and skeletal abnormalities. He showed excellent response to clonazepam and no complications on withdrawing the antiepileptic drugs. Proper diagnosis is of great therapeutic relevance and is based on high degree of suspicion.