Movement Disorders Associated With Radiotherapy and Surgical Procedures.

Occasionally, movement disorders can occur following interventional procedures including but not limited to radiotherapy, dental procedures, and cardiac, cerebral and spinal surgeries. The majority of these disorders tend to be unexpected sequelae with variable phenomenology and latency, and they can often be far more disabling than the primary disease for which the procedure was performed. Owing to poor knowledge and awareness of the problem, delays in diagnosing the condition are common, as are misdiagnoses as functional movement disorders. This narrative review discusses the phenomenology, pathophysiology, and potential treatments of various movement disorders caused by interventional procedures such as radiotherapy and neurological and non-neurological surgeries and procedures.

Surgical Outcomes in Rare Movement Disorders: A Report of Seventeen Patients from India and Review of Literature.

Background: Rare movement disorders (RMDs) throw remarkable challenges to their appropriate management particularly when they are medically refractory. We studied the outcome of functional neurosurgery among patients with RMDs. Methods: Retrospective chart-review from 2006 to 2021 of patients with RMDs who underwent either Deep brain Stimulation (DBS) or lesional surgeries in the department of Neurology and Neurosurgery at a tertiary care centre. Results: Seventeen patients were included. Generalized dystonia (11 patients, 64.7%) and tremor (5 patients, 29.4%) were the most common indication for surgery whereas, Wilson's disease (8 patients, 47.1%) and Neurodegeneration with brain iron accumulation (5 patients, 29.4%) were the most common aetiology. Sixteen patients (94.1%) had objective clinical improvement. Significant improvement was noted in the dystonia motor scores both at 6-months and 12-months follow-up (n = 11, p-value of <0.01 and 0.01 respectively). Comparison between DBS and lesional surgery showed no significant difference in the outcomes (p = 0.95 at 6-months and p = 0.53 at 12-months), with slight worsening of scores in the DBS arm at 12-months. Among five patients of refractory tremor with Wilson's disease, there was remarkable improvement in the tremor scores by 85.0 ± 7.8% at the last follow-up. Speech impairment was the main complication observed with most of the other adverse events either transient or reversible. Discussion: Surgical options should be contemplated among patients with disabling medically refractory RMDs irrespective of the aetiology. Key to success lies in appropriate patient selection. In situations when DBS is not feasible, lesional surgeries can offer an excellent alternative with comparable efficacy and safety.

Utility of Clinical Exome Sequencing in Dystonia: A Single-Center Study From India.

OBJECTIVE: With the use of next-generation sequencing in clinical practice, several genetic etiologies of dystonia have been identified. This study aimed to ascertain the utility of clinical exome sequencing (CES) in dystonia and factors suggestive of a genetic etiology. METHODS: This study was a retrospective chart review of patients with dystonia who had undergone CES for the evaluation of dystonia. RESULTS: Forty-eight patients (35 males, 46 families) with dystonia were studied, with a mean age at onset of 16.0 ± 14.1 (1-58) years. A pathogenic/likely pathogenic variant was found in 20 patients (41.7%) among which 14 patients (29.2%) carried a novel variant. CES was more likely to detect a genetic diagnosis in patients with an early age at onset, i.e., ≤ 20 years. CONCLUSION: CES is a useful tool in the diagnostic evaluation of dystonia, with a yield of close to 40%. Patients with an earlier age at onset have a higher likelihood of having dystonia due to a genetic cause than those with a later age at onset.

Prodromal emesis in MOG-antibody associated disorder.

BACKGROUND: Exclusive emesis has been observed in few patients of MOG-associated disorder (MOGAD). OBJECTIVES: To study the occurrence of emesis in patients of Demyelinating disorders and determine their clinical and radiological features. METHODS AND RESULTS: Medical records of 551 patients of CNS demyelinating disorders were reviewed. Exclusive emesis without hiccups was observed in 1 (0.1%) patient of MS, 17 (6.5%) patients of MOGAD while none were observed in patients of AQP4-ab associated disorders (p < 0.001). There were 17(M:F-8:9) patients with exclusive emesis in MOGAD in 58.8% pediatric age group, adults (35.3%) and late-onset (5.9%). ADEMON (acute demyelinating encephalomyelitis -ADEM followed by optic neuritis) was observed in 7 patients. Preceding clinical syndrome was ON (41.2%), brainstem syndrome (BS) (23.5%), involvement of both ON and BS in 23.5%, myelopathy (11.8%). MRI analysis showed combination of lesions affecting the brainstem (11), optic nerve (10), juxtacortical white matter (10) and periventricular lesions (3). Odds ratio for the presence of ADEM, lesions in medulla, pons, MCP or any of the three areas was found to be significant. CONCLUSIONS: Exclusive emesis without hiccups appears to be common in MOG-antibody associated disorder and may occur as a prodromal illness or exclusive clinical episode. It is known to occur most commonly in association with ADEM and/or Optic neuritis.

Clinical and Imaging Profile of Patients with Joubert Syndrome.

OBJECTIVE: Joubert syndrome (JS) is a rare syndrome characterized by ataxia and the molar tooth sign (MTS) on imaging. The present study aims to explore the clinical and radiological features in a cohort of patients with JS. METHODS: This was a retrospective chart review of patients with JS evaluated by movement disorder specialists. RESULTS: Nine patients were included in the study. All patients had facial dysmorphism and ocular abnormalities, and 4 patients had dystonia. Ocular tilt reaction and alternate skew deviation (66%) were the most common ocular abnormalities. Horizontally aligned superior cerebellar peduncles were observed in all four patients with diffusion tensor imaging, with a lack of decussation in three. Exome sequencing performed in four patients revealed novel variants in the MKS1, CPLANE1, and PIBF1 genes. CONCLUSION: Facial dysmorphism, ocular abnormalities and classical imaging findings were observed in all patients with JS. Apart from ataxia, dystonia and myoclonus are other movement disorders observed in JS.

Clinical characteristics, treatment and long-term prognosis in patients with anti-NMDAR encephalitis.

OBJECTIVES: We aimed to (i) analyse the clinical characteristics, treatment outcome and long-term prognosis of anti-NMDAR encephalitis and (ii) study the differences between paediatric and adult patients. METHODS: This was a chart review of all patients with anti-NMDAR encephalitis. RESULTS: There were 28 patients with 18 patients belonging to the paediatric (<18 years) age group. There was female (94%) preponderance in the paediatric age group, while in adult patients, there was no gender predilection (p=0.006). There was no significant difference in clinical feature, outcome or number of relapses between paediatric and adult population groups. MRI brain was abnormal in 53% of patients. Among the 15 patients with MRI abnormalities at the onset, 53% had poor functional outcome at 1 year, while in 12 patients with normal initial MRI brain, only 8% had poor functional outcome at 1 year (p =0.01). Nearly 53% of patients with abnormal MRI at presentation had at least one clinical relapse within 2 years while in patients with normal MRI at presentation, 15% had a clinical relapse (p=0.037). EEG abnormalities were noticed in 71% of patients; among them, 40 and 15% had poor functional outcome at 1 and 2 years respectively. In comparison, those with normal first EEG at onset, 12% had poor functional outcome at 2 years (p=0.57). CONCLUSIONS: Both paediatric and adult patients presented with similar clinical features but the paediatric population had female preponderance. The functional outcome and number of relapse were comparable in both the paediatric and adult groups. Patients with parenchymal changes on MRI and abnormal EEG showed poorer response compared to those with normal MRI and/or EEG at the onset. Patients have lesser severity of symptoms at relapse than in the first episode. An early diagnosis and treatment are essential for better long-term functional outcome.

Cervical Myeloradiculopathy and Atlantoaxial Instability in Cervical Dystonia.

OBJECTIVE: Atlantoaxial instability, although rarely reported in the literature, can be associated with cervical dystonia (CD) and may lead to compression of the cord at the craniovertebral junction. We present a case series of 4 patients of longstanding CD with neurologic complications. Treatment strategies and challenges are discussed. METHODS: Retrospective analysis of 4 cases of longstanding CD with complications of myelopathy or radiculopathy. RESULTS: The average age at onset of complications was 28 years (range, 17-37). The average duration of CD was 23.75 years. Narrowing of the craniovertebral junction was seen in 3 patients, of which 2 had os odontoideum, and 1 had rotational malalignment at the atlantoaxial joint. One patient had disc desiccation with bulge and intramedullary signal changes in the cord at C3-4 level. Medical treatment was not satisfactory, but botulinum toxin was partly useful in all. One patient had sequelae of myelopathy and did recover partially after deep brain stimulation. Of the 2 patients who underwent surgical fixation with a fusion of the spine, one improved, and the other had no improvement due to irreversible cord damage. The overall outcome was satisfactory only in 2 patients. CONCLUSIONS: Early-onset CD can lead to cord complications at a young age and at higher levels of the cervical spine and at the cervicovertebral junction. Comprehensive management by a multidisciplinary team is crucial to prevent complications early.

Myelin oligodendrocyte glycoprotein-antibody-associated disorder: a new inflammatory CNS demyelinating disorder.

BACKGROUND AND AIMS: Myelin oligodendrocyte glycoprotein (MOG) is an oligodendrocytopathy resulting in demyelination. We aimed to determine the frequency of MOG-associated disorders (MOGAD), its various clinical phenotypes, and imaging characteristics. METHODS: All patients with MOGAD were included. Description of the various clinical phenotypes, investigation profile, therapeutic response, differences between pediatric and adult-onset neurological disorders, determination of poor prognostic factors was done. RESULTS: The study population consisted of 93 (M:F = 45:48) (Pediatric:40, Adult-onset:47, Late-onset:7) patients with a median age of 21 years. Among the 263 demyelinating episodes; 45.8% were optic neuritis (ON), 22.8% were myelopathy, 17.1% were brainstem, 7.6% were acute demyelinating encephalomyelitis(ADEM), 4.2% were opticomyelopathy and 2.3% with cerebral manifestations. There was exclusive vomiting in 24.7% prior to onset of clinical syndrome, none of them had area postrema involvement. ADEM was exclusively seen in pediatric patients. Poor prognostic indicators included: (i) incomplete recovery from an acute attack, (b) brainstem syndrome, (c) ADEM with incomplete recovery, (d) MRI suggestive of leukodystrophy pattern, (e) severe ON, (f) ADEMON. CONCLUSIONS: The Spectrum of MOG-associated disorders is wider affecting the brain (grey and white matter) and the meninges. There are various clinical phenotypes and MRI patterns, recognition of which may help in the determination of therapeutic strategies, and long-term prognosis.

Sialidosis Type I without a Cherry Red Spot- Is There a Genetic Basis?

Sialidosis is an inborn error of metabolism due to a defect in the NEU1 gene and manifests as two phenotypes: mild type I and severe type II. The cherry red spot (CRS) is a characteristic feature in both types of sialidosis; reports of sialidosis without a CRS are rare. We report two cases of genetically confirmed sialidosis type I with a typical presentation of progressive cortical myoclonus and ataxia but without the CRS. A previously reported homozygous pathogenic variant p.Arg294Cys was detected in the first case, and a novel homozygous pathogenic variant p.Arg305Pro was detected in the second case. Additionally, we reviewed the literature describing cases with similar mutations to find a genetic basis for the absence of a CRS. Milder mutation of both alleles detected in both patients may be the reason for the absence of a CRS.

Comparison of effectiveness of trihexyphenidyl and levodopa on motor symptoms in Parkinson's disease.

Despite anti-cholinergics being the oldest type of medication used for the treatment of Parkinson's disease (PD), the mechanism of action and exact benefit is unclear. This study compared the effectiveness of trihexyphenidyl (THP) and levodopa (LD) on motor symptoms in patients with PD. Patients with PD who are currently taking or had taken THP were recruited. UPDRS-III was done following overnight medication OFF state and 30 min, 60 min, 90 min, and 120 min after THP (4 mg). After a forty-eight-hour interval, UPDRS-III was assessed one hour after Levodopa/carbidopa (200/50 mg) in an overnight OFF state. Twenty patients with a mean age of 57.9 ± 7.8 years and mean duration of illness of 5.1 ± 3.6 years were recruited. UPDRS-III score reduction (%) with THP was maximum in the tremor sub-score (53.8 ± 22.8) and was significantly better compared to improvement in total-UPDRS-III (27.0 ± 14.7), bradykinesia-UPDRS-III (22.2 ± 27.2), rigidity-UPDRS-III (29.5 ± 28.0) and axial-UPDRS-III (8.1 ± 13.3) sub-score. In comparison, respective LD improvement was 67.1 ± 22.9 (tremor-UPDRS-III), 61.3 ± 14.4 (total-UPDRS-III), 67.9 ± 32.1 (bradykinesia-UPDRS-III), 65.3 ± 25.5 (rigidity-UPDRS-III) and 50.7 ± 16.0 (axial-UPDRS-III). Improvement (%) in tre-UPDRS-III post-THP was comparable to that of post-LD (53.8 ± 22.8 vs. 67.1 ± 22.9, p = 0.057). Those with same or better tremor response with THP had significantly milder baseline tremor severity than those who had better response with LD (tre-UPDRS-III-OFF, 10.0 ± 2.8 vs. 5.8 ± 4.0, p = 0.013). Both THP and LD showed significant improvement in UPDRS-III. With THP, the maximum degree of improvement was in the tremor sub-score and not significantly different to that obtained by LD. Those with better tremor response on THP had milder tremor severity.

Impact of Prolonged Lockdown due to COVID-19 in Patients with Parkinson's Disease.

BACKGROUND: The COVID-19 pandemic has compelled countries to impose lockdowns to curb the spread. As a result of the lockdown and need for health care services to cater to acute diseases on priority, patients with chronic illnesses such as Parkinson's disease (PD) may be facing several difficulties. AIMS: This study aimed to explore the effects of prolongation of lockdown on patients with PD by evaluating possible problems faced during a lockdown and worsening of symptoms if any. MATERIALS AND METHODS: One hundred patients with PD and their caregivers were contacted. RESULTS: We observed a significant increase in problems faced due to this pandemic, specifically, the inability to access health care, and difficulty procuring medication. Patients also reported worsening of motor symptoms. CONCLUSIONS: The present findings highlight the need for health care systems to consider a plan of action for chronic neurological diseases like PD, which are worsening in the absence of regular hospital visits.

Deep Brain Stimulation Battery Exhaustion during the COVID-19 Pandemic: Crisis within a Crisis.

OBJECTIVE: The novel coronavirus disease (COVID-19) pandemic and public health measures to control it have resulted in unique challenges in the management of patients with deep brain stimulation (DBS). We report our experience with the management of acute worsening of symptoms due to battery exhaustion in 3 patients with DBS. METHODS: Patients with DBS for movement disorders who visited the emergency room due to battery exhaustion during the nationwide lockdown from April to May 2020 were included. RESULTS: Two patients with subthalamic nucleus-DBS for Parkinson's disease (PD) and one with globus pallidus interna-DBS for generalized dystonia presented with acute worsening of symptoms due to battery exhaustion. Urgent battery replacement was performed in both patients with PD. The patient with generalized dystonia was managed with medication adjustment as he chose to defer battery replacement. CONCLUSION: DBS battery replacement can be an emergency. Decisions regarding DBS battery replacement should be individualized during this COVID-19 pandemic.

The Non-Motor Symptom Profile of Progressive Supranuclear Palsy.

OBJECTIVE: Non-motor symptoms (NMSs) significantly contribute to increased morbidity and poor quality of life in patients with parkinsonian disorders. This study aims to explore the profile of NMSs in patients with progressive supranuclear palsy (PSP) using the validated Non-Motor Symptom Scale (NMSS). METHODS: Seventy-six patients with PSP were evaluated in this study. Motor symptoms and NMSs were evaluated using the PSP Rating Scale (PSPRS), Unified Parkinson's Disease Rating Scale-III, Montreal Cognitive Assessment, Hamilton Depression (HAM-D) and Anxiety Rating Scales, Parkinson's Disease Sleep Scale (PDSS) and NMSS. NMS severity and prevalence were also compared between patients with PSP-Richardson syndrome (PSP-RS) and those with PSP-parkinsonism. RESULTS: All subjects in this cohort reported at least 2 NMSs. The most prevalent NMSs in patients with PSP were in the domains of sleep/fatigue, mood/cognition, and sexual function. The least prevalent NMSs were in the domains of cardiovascular including falls, and perceptual problems/hallucinations. Significant correlations were observed between the NMSS scores and HAM-D, PDSS, PSPRS scores and PSPRS sub-scores. The severity of NMSs was unrelated to the duration of illness. Patients with PSP-RS reported a higher severity of drooling, altered smell/taste, depression and altered interest in sex and a higher prevalence of sexual dysfunction. CONCLUSION: NMSs are commonly observed in patients with PSP, and the domains of sleep, mood and sexual function are most commonly affected. These symptoms contribute significantly to disease morbidity, and clinicians should pay adequate attention to identifying and addressing these symptoms.