Pick's Disease Presenting as Tremulous Parkinsonism with Limited Levodopa Response-A Rare Cause of Corticobasal Syndrome.

BACKGROUND: Corticobasal syndrome is a clinical diagnosis and common pathological causes are corticobasal degeneration, progressive supranuclear palsy and Alzheimer's disease. OBJECTIVES: We would like to highlight a rare but important differential of corticobasal syndrome. METHODS: A 78-year-old female had a 4-year history of predominantly right-hand rest tremor, worsening of handwriting but no change in cognition. The clinical examination showed right upper limb postural and kinetic tremor, mild wrist rigidity and reduced amplitude of right-sided finger tapping. She was initially diagnosed as idiopathic Parkinson's disease. Five years after onset of symptoms, she demonstrated bilateral myoclonic jerks and right upper limb dystonic posturing. She could not copy movements with the right hand. The magnetic resonance imaging (MRI) revealed disproportionate atrophy in the parietal lobes bilaterally. The clinical diagnosis was changed to probable corticobasal syndrome. She passed away 11 years from onset of symptoms at the age of 85 years. She underwent a post-mortem. RESULTS: The anterior and posterior frontal cortex, anterior cingulate, temporal neocortex, hippocampus and amygdaloid complex demonstrated considerable tau-related pathology consisting of a dense background of neuropil threads, and rounded, paranuclear neuronal inclusions consistent with Pick bodies. The immunostaining for three microtubule binding domain repeats (3R) tau performed on sections from the frontal and temporal lobes, basal ganglia and midbrain highlighted several inclusions whilst no 4R tau was observed. She was finally diagnosed with Pick's disease. CONCLUSIONS: Pick's disease can rarely present with clinical features of corticobasal syndrome.

Corneal confocal microscopy demonstrates varying degrees of neurodegeneration in atypical parkinsonian disorders.

OBJECTIVE: We have used corneal confocal microscopy (CCM) to identify corneal nerve loss as a potential marker of neurodegeneration in participants with Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). METHODS: Patients with PD (n = 19), PSP (n = 11), MSA (n = 8) and healthy controls (n = 18) underwent neurological assessment and CCM. RESULTS: Corneal nerve fibre density was significantly lower in participants with PD (p = 0.005), PSP (p = 0.005) and MSA (p = 0.0003) compared to controls. Corneal nerve branch density was significantly lower in participants with PD (p = 0.01) and MSA (p = 0.019), but not in participants with PSP (p = 0.662), compared to controls. Corneal nerve fibre length was significantly lower in participants with PD (p = 0.002) and MSA (p = 0.001) but not in participants with PSP (p = 0.191) compared to controls. CONCLUSION: CCM detects corneal nerve loss in participants with PD and MSA and to a lesser extent in PSP compared to healthy controls.

Frontotemporal Dementia-Parkinsonism Due to MAPT Gene Variant Presenting with Rest and Action Tremor.

A 50-year-old male presented with a four-year history of gradually progressive rest tremor in the distal right lower limb and then spreading to the left lower limb in last 10-12 months. He developed right arm rest and action tremor two years later. Magnetic resonance imaging scans showed progressive frontotemporal and asymmetrical mesial temporal atrophy. Genetic testing revealed a heterozygous c.915+16C>T pathogenic variant in intron 9 of the MAPT gene. Presentation with rest tremor should not exclude frontotemporal dementia-parkinsonism due to a MAPT variant as a differential diagnosis though rest tremor is a rare presentation.

Generalized Dystonia Due to a Pathogenic THAP1 Variant Showing Sustained Response to Globus Pallidus Deep Brain Stimulation.

A 21-year-old woman of south Asian origin presented with cervical dystonia which had progressed over the previous three years. Her symptoms started as writer's cramp since the age of seven years. She did not respond to medications and needed botulinum toxin injection for generalised dystonia. Subsequent whole genome sequencing revealed a likely pathogenic c.98G>A p.(Cys33Tyr) heterozygous variant in the THAP1 gene. She underwent bilateral posteroventral globus pallidus interna (GPi) deep brain stimulation (Medtronic Activa PC) implantation at the age of thirty-one years. She responded well to the deep brain stimulation even after more than 8 years post-surgery though she needs botulinum toxin injection for her cervical dystonia.

Pure Autonomic Failure-A Localized Alpha Synucleinopathy with a Potential for Conversion to More Extensive Alpha Synucleinopathies.

Pure autonomic failure (PAF) is an alpha synucleinopathy with predominant involvement of the autonomic ganglia and peripheral nerves. The hallmark clinical feature is orthostatic hypotension. However, genitourinary, sudomotor, and cardiac involvement is also common. Many patients also develop supine hypertension. Almost a quarter of patients can phenoconvert or evolve into Parkinson's disease, multiple system atrophy, and Lewy body dementia in the future. Early severe bladder involvement, higher supine noradrenaline level, early motor involvement, and dream enactment behavior increase the risk of phenoconversion. The diagnosis is confirmed via autonomic function testing and serum noradrenaline measurement. The treatment is mainly supportive. The non-pharmacological treatment includes adequate fluid, dietary salt, compression stockings, and abdominal binders. The drug therapies to improve blood pressure include midodrine, fludrocortisone, pyridostigmine, and droxidopa. The diagnostic criteria need to be updated to incorporate the recent understandings. The treatment of orthostatic hypotension and supine hypertension is mainly based on case series and anecdotal reports. Randomized control trials are needed to ascertain the best treatment strategies for PAF.

Early Onset Degenerative Parkinsonism - Consider SPG7 Mutation.

A 43-year-old man presented with ataxia and stiffness of lower limbs for approximately last 10 years. The clinical examination revealed bilateral parkinsonism The magnetic resonance imaging of the brain and spine showed no structural abnormality to explain his symptoms. However, the dopamine transporter scan showed abnormal tracer uptake in both basal ganglia, suggestive of degenerative parkinsonism. The next generation sequencing of spastic paraparesis gene panel revealed probably pathogenic novel mutation in the SPG7 gene. Though the exact mechanism of parkinsonism in SPG 7 mutation is unclear, mitochondrial dysfunction and oxidative stress seem to play a key role. SPG7 mutation should be considered as a cause of early onset degenerative parkinsonism when no alternative explanation can be found.

C19orf12 mutation causing mitochondrial membrane-protein Associated Neurodegeneration masquerading as spastic paraplegia.

Mitochondrial Membrane-protein Associated Neurodegeneration (MPAN) is a rare disease, caused by C19orf12 mutations and up to 29 different mutations have been described. We report a young woman presented with spastic paraparesis due to C19orf12 gene. MPAN presenting like Hereditary spastic paraplegia-43 is rare and the genetic mutation had been described only once in the literature.

Diaphragmatic paralysis resulting in respiratory failure as a feature of hepatitis E virus-associated neuralgic amyotrophy.

Hepatitis E virus (HEV)-associated neuralgic amyotrophy (NA) is often bilateral and severe, involving structures outside the brachial plexus, such as the phrenic nerves or the lumbosacral plexus. We report a case of an HEV-positive man who had presented with brachial neuritis, with significant phrenic nerve involvement, resulting in diaphragmatic paralysis requiring non-invasive ventilation. Prognosis of HEV-associated NA is often unfavourable and recovery is usually incomplete. Identifying HEV-associated NA early could potentially aid in prognostication and management planning, as clinicians and patients would be expectant of its potential features and severity. Respiratory function should be monitored in patients with HEV who suffer from NA, as diaphragmatic paralysis could potentially lead to severe respiration difficulties requiring ventilatory support.

Palatal Tremor - Pathophysiology, Clinical Features, Investigations, Management and Future Challenges.

Background: Palatal tremor is involuntary, rhythmic and oscillatory movement of the soft palate. Palatal tremor can be classified into three subtypes; essential, symptomatic and palatal tremor associated with progressive ataxia. Methods: A thorough Pubmed search was conducted to look for the original articles, reviews, letters to editor, case reports, and teaching neuroimages, with the keywords "essential", "symptomatic palatal tremor", "myoclonus", "ataxia", "hypertrophic", "olivary" and "degeneration". Results: Essential palatal tremor is due to contraction of the tensor veli palatini muscle, supplied by the 5th cranial nerve. Symptomatic palatal tremor occurs due to the contraction of the levator veli palatini muscle, supplied by the 9%th and 10%th cranial nerves. Essential palatal tremor is idiopathic, while symptomatic palatal tremor occurs due to infarction, bleed or tumor within the Guillain-Mollaret triangle. Progressive ataxia and palatal tremor can be familial or idiopathic. Symptomatic palatal tremor and sporadic progressive ataxia with palatal tremor show signal changes in inferior olive of medulla in magnetic resonance imaging. The treatment options available for essential palatal tremor are clonazepam, lamotrigine, sodium valproate, flunarizine and botulinum toxin. The treatment of symptomatic palatal tremor involves the treatment of the underlying cause. Discussion: Further studies are required to understand the cause and pathophysiology of Essential palatal tremor and progressive ataxia and palatal tremor. Similarly, the link between tauopathy and palatal tremor associated progressive ataxia needs to be explored further. Oscillopsia and progressive ataxia are more debilitating than palatal tremor and needs new treatment approaches.

Analysis of the Effect of Dopamine Transporter Scan on the Diagnosis and Management in a Tertiary Neurology Center.

BACKGROUND AND PURPOSE: The dopamine transporter scan or DaT scan is abnormal in presynaptic parkinsonism but normal in nondegenerative or postsynaptic parkinsonism. In this study, we tried to ascertain the impact of DaT scan on the diagnosis and clinical management and if the semiquantitative analysis of the DaT scans has any correlation with the clinical symptoms. METHODS: The electronic and nonelectronic records of patients of Plymouth Hospital NHS Trust, United Kingdom, from 2011 to 2015 were studied to find the indication, outcome, and the impact of the scan on the management of patients. The DaT scan results were assessed visually and semiquantitatively by the Department of Nuclear Medicine. The available data were statistically analyzed with the help of Microsoft XL2010 and GraphPad software. RESULTS: A total of 258 people had DaT scan. The scan results suggested an alternate diagnosis in 50.5% of clinically diagnosed patients with Parkinson disease. Similarly, DaT scan changed the diagnosis of 40% of patients with clinical diagnosis of vascular parkinsonism, 25% of clinically diagnosed drug-induced parkinsonism, and 54% of patients with possible Lewy body dementia. Visual assessment of the DaT scan revealed that more than 60% had grade 2 abnormalities. The distribution volume ratio, a semiquantitative tool for tracer uptake, was significantly less in the patients with akinetic-rigid subtype of Parkinson disease in comparison to a tremor predominant subtype. CONCLUSIONS: Dopamine transporter scan had a significant impact in diagnosis and management.