Analysis of a distinct speech disorder seen in chronic manganese toxicity following Ephedrone abuse

INTRODUCTION: In the last fifteen years a new cause of chronic manganese toxicity has been recognized. It follows recreational intravenous injections of Ephedrone, synthesized from a cold remedies contained pseudoephedrine. Potassium permanganate is used as an oxidant. It presents with severe parkinsonism-dystonia and a characteristic dysarthria. OBJECTIVES: We performed a focus perceptual study of dysarthria in Ephedrone induced parkinsonism and compared the findings with the speech disorders seen in Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP). METHODS: A digital voice recording, perceptual speech analysis (Darley, 1975) [18], serial neurological assessment and Brain Magnetic Resonance (MR) imaging were performed at the Lviv regional Clinical Hospital. The results were analysed at the Institute of Neurology in London. RESULTS: Dysarthria developed after 8.5 ± 3.2 months of daily intravenous Ephedrone abuse and was an initial symptom in a third of cases. It was characterised by a robotic-flat prosody, whispering or continuous phonation, an inability to regulate pitch and volume, frozen lip articulation, a variable degree of dystonic tightness, difficulties in speech initiation and palladia, There was no nasality and swallowing was normal. In some patients speech deteriorated even after the discontinuation of Ephedrone. MR imaging, performed soon after drug cessation showed T1 signal hyperintesity in striatum and pallidum, especially in the Globus Pallidum interna. CONCLUSION: Ephedrone induced chronic manganese toxicity can lead to a mixed hypokinetic-dystonic dysarthria with a distinct dystonic pattern. Perceptual speech analysis can be a helpful ancillary investigation in the differential diagnosis of parkinsonism, and may permit the recognition of chronic manganese toxicity

The first experience of using kinesiotaping in the treatment of symphysiopathy in women in the second half of pregnancy

The aim of the study - to evaluate the effectiveness of kinesiotaping in reducing the level of pain in pregnant symphysiopathyЦель исследования - оценить эффективность кинезиотейпирования в снижении уровня боли при симфизиопатии беременны

Pros and cons of a prion-like pathogenesis in Parkinson's disease

Background: Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder which affects widespread areas of the brainstem, basal ganglia and cerebral cortex. A number of proteins are known to accumulate in parkinsonian brains including ubiquitin and alpha-synuclein. Prion diseases are sporadic, genetic or infectious disorders with various clinical and histopathological features caused by prion proteins as infectious proteinaceous particles transmitting a misfolded protein configuration through brain tissue. The most important form is Creutzfeldt-Jakob disease which is associated with a self-propagating pathological precursor form of the prion protein that is physiologically widely distributed in the central nervous system. Discussion: It has recently been found that alpha-synuclein may behave similarly to the prion precursor and propagate between cells. The post-mortem proof of alpha-synuclein containing Lewy bodies in embryonic dopamine cells transplants in PD patient suggests that the misfolded protein might be transmitted from the diseased host to donor neurons reminiscent of prion behavior. The involvement of the basal ganglia and brainstem in the degenerative process are other congruencies between Parkinson's and Creutzfeldt-Jakob disease. However, a number of issues advise caution before categorizing Parkinson's disease as a prion disorder, because clinical appearance, brain imaging, cerebrospinal fluid and neuropathological findings exhibit fundamental differences between both disease entities. Most of all, infectiousness, a crucial hallmark of prion diseases, has never been observed in PD so far. Moreover, the cellular propagation of the prion protein has not been clearly defined and it is, therefore, difficult to assess the molecular similarities between the two disease entities. Summary: At the current state of knowledge, the molecular pathways of transmissible pathogenic proteins are not yet fully understood. Their exact involvement in the pathophysiology of prion disorders and neurodegenerative diseases has to be further investigated in order to elucidate a possible overlap between both disease categories that are currently regarded as distinct entities

Subregional 6-[18F]fluoro-ʟ-m-tyrosine Uptake in the Striatum in Parkinson's Disease

<p>Abstract</p> <p>Background</p> <p>In idiopathic Parkinson's disease (PD) the clinical features are heterogeneous and include different predominant symptoms. The aim of the present study was to determine the relationship between subregional aromatic l-amino acid decarboxylase (AADC) activity in the striatum and the cardinal motor symptoms of PD using high-resolution positron emission tomography (PET) with an AADC tracer, 6-[¹⁸F]fluoro-ʟ-<it>m</it>-tyrosine (FMT).</p> <p>Methods</p> <p>We assessed 101 patients with PD and 19 healthy volunteers. PD was diagnosed based on the UK Brain Bank criteria by two experts on movement disorders. Motor symptoms were measured with the Unified Parkinson's Disease Rating Scale (UPDRS). FMT uptake in the subregions of the striatum was analyzed using semi-automated software for region-of-interest demarcation on co-registered magnetic resonance images.</p> <p>Results</p> <p>In all PD patients, FMT uptake was decreased in the posterior putamen regardless of predominant motor symptoms and disease duration. Smaller uptake values were found in the putamen contralateral to the side with more affected limbs. The severity of bradykinesia, rigidity, and axial symptoms was correlated with the decrease of FMT uptake in the putamen, particularly in the anterior part. No significant correlation was observed between tremors and FMT uptake.</p> <p>Conclusions</p> <p>Decrease of FMT uptake in the posterior putamen appears to be most sensitive in mild PD and uptake in the anterior putamen may reflect the severity of main motor symptoms, except for tremor.</p

The ongoing pursuit of neuroprotective therapies in Parkinson disease

Many agents developed for neuroprotective treatment of Parkinson disease (PD) have shown great promise in the laboratory, but none have translated to positive results in patients with PD. Potential neuroprotective drugs, such as ubiquinone, creatine and PYM50028, have failed to show any clinical benefits in recent high-profile clinical trials. This 'failure to translate' is likely to be related primarily to our incomplete understanding of the pathogenic mechanisms underlying PD, and excessive reliance on data from toxin-based animal models to judge which agents should be selected for clinical trials. Restricted resources inevitably mean that difficult compromises must be made in terms of trial design, and reliable estimation of efficacy is further hampered by the absence of validated biomarkers of disease progression. Drug development in PD dementia has been mostly unsuccessful; however, emerging biochemical, genetic and pathological evidence suggests a link between tau and amyloid-β deposition and cognitive decline in PD, potentially opening up new possibilities for therapeutic intervention. This Review discusses the most important 'druggable' disease mechanisms in PD, as well as the most-promising drugs that are being evaluated for their potential efficiency in treatment of motor and cognitive impairments in PD

RÜLFS CRAMP AND OTHER PAROXYSMAL DYSKINESIA

Paroxysmal dyskinesia comprise a significant and fascinating part of movement disorders, which represent a diagnostic challenge for neurologists working on the borderlands of psychiatry and epilepsy. The current classification based on the relation of attacks to a movement is supported by the response to treatment and genetic difference. We reviewed clinical characteristics and the main advances in genetics of these unique, usually hereditary diseases. Clinical diagnosis remains the key to the treatment choice. Psychogenic causes are common in sporadic cases, but paroxysmal dyskinesia secondary to systemic or primary neurological disorders should not be missed and warrant careful investigation

Per-oral image guided gastrojejunostomy insertion for levodopa-carbidopa intestinal gel in Parkinson's disease is safe and may be advantageous.

BACKGROUND: Procedural aspects and complications of gastrojejunostomy insertion are important considerations in the use of levodopa-carbidopa intestinal gel therapy (LCIG) and may limit uptake. We describe our experience of using per-oral image guided gastrojejunostomy (PIG-J) which avoids the need for endoscopy and routine sedation in percutaneous endoscopic gastrojejunostomy (PEG-J) and allows more secure tube placement than radiologically inserted gastrojejunostomy techniques. METHODS: We describe a case series of 32 patients undergoing PIG-J insertion for LCIG therapy in a single centre. Under local anaesthetic, a fluoroscopy-guided gastric puncture allows access for the guidewire which is then used to pull through the gastrostomy tube allowing for secure fixation, followed by placement of the gastrojejunal extension. RESULTS: Between December 2015 to April 2020, 32/34 patients referred for PIG-J underwent this procedure successfully, 2 cases unsuccessful due to technical considerations. One patient developed delirium following successful implantation. Ten patients (31%) required a replacement tube due to blockage or displacement within the first 12 months of placement, including 2 patients who needed more than one replacement. Minor complications occurred in 10 other patients (31%), including infection (9 patients); a small haematoma not requiring intervention who later developed an infection (1 patient); and peri-stomal acid leakage (1 patient). CONCLUSION: In summary, PIG-J insertion is safe with a similar complication rate to traditional PEG-J, well tolerated and effective for use in LCIG administration. This may widen access to LCIG for PD patients who may not be suitable or unable to tolerate PEG-J

A 30-year history of MPAN case from Russia

We present a patient with progressive spastic ataxia, with dystonia and anarthria undiagnosed until detailed genetic analysis revealed an MPAN mutation. Highlighting the worldwide MPAN distribution, a 30 year history of absent diagnosis and the impact and cost saving of an early but detailed genetic analysis in complex progressive movement disorders, particularly the anarthric NBIA group

The significance of α-Synuclein, Amyloid-β and Tau pathologies in Parkinson's disease progression and related dementia

Background: Dementia is one of the milestones of advanced Parkinson’s disease (PD), with its neuropathological substrate still being a matter of debate, particularly regarding its potential mechanistic implications. Objective: The aim of this study was to review the relative importance of Lewyrelated α-synuclein and Alzheimer’s tau and amyloid-β (Aβ) pathologies in disease progression and dementia in PD. Methods: We reviewed studies conducted at the Queen Square Brain Bank, Institute of Neurology, University College London, using large PD cohorts. Results: Cortical Lewy- and Alzheimer-type pathologies are associated with milestones of poorer prognosis and with non-tremor predominance, which have been, in turn, linked to dementia. The combination of these pathologies is the most robust neuropathological substrate of PD-related dementia, with cortical Aβ burden determining a faster progression to dementia. Conclusion: The shared relevance of these pathologies in PD progression and dementia is in line with experimental data suggesting synergism between α-synuclein, tau and Aβ and with studies testing these proteins as disease biomarkers, hence favouring the eventual testing of therapeutic strategies targeting these proteins in PD.</p

The significance of α-Synuclein, Amyloid-β and Tau pathologies in Parkinson's disease progression and related dementia

Background: Dementia is one of the milestones of advanced Parkinson’s disease (PD), with its neuropathological substrate still being a matter of debate, particularly regarding its potential mechanistic implications. Objective: The aim of this study was to review the relative importance of Lewyrelated α-synuclein and Alzheimer’s tau and amyloid-β (Aβ) pathologies in disease progression and dementia in PD. Methods: We reviewed studies conducted at the Queen Square Brain Bank, Institute of Neurology, University College London, using large PD cohorts. Results: Cortical Lewy- and Alzheimer-type pathologies are associated with milestones of poorer prognosis and with non-tremor predominance, which have been, in turn, linked to dementia. The combination of these pathologies is the most robust neuropathological substrate of PD-related dementia, with cortical Aβ burden determining a faster progression to dementia. Conclusion: The shared relevance of these pathologies in PD progression and dementia is in line with experimental data suggesting synergism between α-synuclein, tau and Aβ and with studies testing these proteins as disease biomarkers, hence favouring the eventual testing of therapeutic strategies targeting these proteins in PD.</p