Lack of Accredited Clinical Training in Movement Disorders in Europe, Egypt, and Tunisia

Background: Little information is available on the official postgraduate and subspecialty training programs in movement disorders (MD) in Europe and North Africa. Objective: To survey the accessible MD clinical training in these regions. Methods: We designed a survey on clinical training in MD in different medical fields, at postgraduate and specialized levels. We assessed the characteristics of the participants and the facilities for MD care in their respective countries. We examined whether there are structured, or even accredited postgraduate, or subspecialty MD training programs in neurology, neurosurgery, internal medicine, geriatrics, neuroradiology, neuropediatrics, and general practice. Participants also shared their suggestions and needs. Results: The survey was completed in 31/49 countries. Structured postgraduate MD programs in neurology exist in 20 countries; structured neurology subspecialty training exists in 14 countries and is being developed in two additional countries. Certified neurology subspecialty training was reported to exist in 7 countries. Recommended reading lists, printed books, and other materials are the most popular educational tools, while courses, lectures, webinars, and case presentations are the most popular learning formats. Mandatory activities and skills to be certified were not defined in 15/31 countries. Most participants expressed their need for a mandatory postgraduate MD program and for certified MD sub-specialization programs in neurology. Conclusion: Certified postgraduate and subspecialty training exists only in a minority of European countries and was not found in the surveyed Egypt and Tunisia. MD training should be improved in many countries.Peer reviewe

Ubiquitin and Parkinson's disease through the looking glass of Genetics

Biochemical alterations found in the brains of Parkinson's disease (PD) patients indicate that cellular stress is a major driver of dopaminergic neuronal loss. Oxidative stress, mitochondrial dysfunction, and ER stress lead to impairment of the homeostatic regulation of protein quality control pathways with a consequent increase in protein misfolding and aggregation and failure of the protein degradation machinery. Ubiquitin signalling plays a central role in protein quality control; however, prior to genetic advances, the detailed mechanisms of how impairment in the ubiquitin system was linked to PD remained mysterious. The discovery of mutations in the α-synuclein gene, which encodes the main protein misfolded in PD aggregates, together with mutations in genes encoding ubiquitin regulatory molecules, including PTEN-induced kinase 1 (PINK1), Parkin, and FBX07, has provided an opportunity to dissect out the molecular basis of ubiquitin signalling disruption in PD, and this knowledge will be critical for developing novel therapeutic strategies in PD that target the ubiquitin system

Neuroprotective Treatments In Parkinson'S Disease

Parkinson's disease (PD) is a progressive disease due to dopaminergic cell lass in the substantia nigra and dopaminergic terminal lost in the striatum, which is the projection area of substantia nigra. It is characterized by resting tremor, bradykinesia, rigidity, and postural instability. In PD, non-motor symptoms such as cognitive impairment, anhedonia, apathy, and autonomic nervous system impairments affect quality of life as much as motor symptoms. PD may affect multiple systems and the underlying mechanisms are not known. However, developing new methods of treatment to slow or stop the rate of disease progression, to lessen or to cure the symptoms is crucial. The aim of this review was to discuss the alternative treatments that may be useful for both motor and non-motor symptoms. Symptomatic treatments with dopaminergic drugs aim to relieve motor symptoms and to increase the patient's life standards for a limited time. However, possible neuroprotective treatments that inhibit neuronal cell death can extend life span and provide higher quality of life. Lewy bodies, which are formed mainly from misfolded and native alpha-synuclein protein, is a pathologic hallmark of PD. Therefore, inhibiting the protein misfolding or clearing the aggregates could be a promising new therapeutic approach for the disease.WoSScopu

Spectral Analysis of Lithium Tremor

Introduction: Lithium has proven efficacy in bipolar affective disorder (BAD) but induces tremor as a side effect in a quarter of patients. Lithium tremor (LT) shares some clinical characteristics of essential tremor (ET) and Parkinson’s disease tremor (PT), which might cause difficulties in differential diagnosis. Furthermore, current knowledge of LT is lacking detailed electrophysiological characterization. Here, we present detailed spectral attributes of accelerometric tremor recordings as a diagnostic tool for LT. Methods: 10 patients (7 males, 3 females) between ages of 29–68, who were on lithium for BAD for 2–12 years, were evaluated for hand tremor with the spectral analysis of accelerometric recordings with different postures. Tremor severity was rated clinically on WHIGET (Washington Heights-Inwood Genetic Study of Essential Tremor) scale. Results were analyzed in comparison to results of ET (n=19) and PT (n=19) patients from our database. Results: LT was most prominent at extensor postures with an average peak frequency (PF) of 8.0±0.3 Hz and an extremely low amplitude, high harmonic components and high noise level. The average PF of LT was similar to that of ET (7.3±0.4 Hz), but higher than that of PT (5.3±0.2 Hz) (p<0.0001). With weight loading, the PF of LT showed an increase of 1.3 Hz. Average amplitude of PT was higher than that of both LT and ET (p<0.0001); harmonic components of LT was comparable to PT whereas noise levels were similar to that of ET. Mean WHIGET score of LT (6.5±0.5) was significantly lower than that of ET (13.1±1) (p<0.0001). Conclusion: Electrophysiological features detected by accelerometry may help in differential diagnosis of LT from ET and PT. Keywords: Lithium tremor, accelerometry, tremorogram, peak frequency, harmonic component

Striatal Neurotransmitter Release-Related Presynaptic Proteins In L-Dopa Induced Dyskinesia In A Model Of Parkinsonism

Introduction: In Parkinson's disease, L-dopa-induced dyskinesia (LID) and motor fluctuations incapacitate patients as much as the disease itself. Many studies demonstrated that postsynaptic alterations and striatal synaptic plasticity changes play a role in LID development. Here, we aimed to study the role of striatal presynaptic proteins in LID pathogenesis. Methods: For this purpose, 6-hydroxydopamine model of parkinsonism was used. To induce LID, these rats were treated with intraperitoneal injections of L-dopa 25 mg/kg with benserazide 6.25 mg/kg b.i.d for 21 days. Rats with parkinsonism treated with saline and control rats treated with saline or L-dopa/ benserazide were also included. Behaviors of rats were videotaped and scored according to dyskinesia scale. Striatal tissue was analysed with immunofluorescence staining and immunoblotting to confirm loss of tyrosine hydroxylase (TH) expression due to dopaminergic denervation and to explore the alterations in the expression of presynaptic proteins, secretogranin 2 (SG2), synaptophysin (Syp) and synaptotagmin 7 (Syt7). Result: LID developed only in rats with parkinsonism treated with chronic L-dopa. Immunofluorescence and immunoblotting studies for TH confirmed depletion of dopaminergic neurons, which was also strongly and negatively correlated with severity of LID. Striatal SG2 and Syp levels were found increased in parkinsonian rats. Chronic L-dopa treatment further increased SG2 levels in denervated striatum. Striatal SG 2 level showed a significant moderate, positive correlation with LID severity Immunofluorescence studies also demonstrated increased expression of these presynaptic proteins in the denervated striatum. Conclusion: As, severity of LID was clearly correlated with striatal 562 expression; there is supposedly a functional relationship between striatal SG2 and LID. Further studies are needed to find out molecular mechanisms linking increased SG2 expression and LID.Wo

Macrocytic Anemia In Lesch-Nyhan Disease And Its Variants

Purpose: Lesch-Nyhan disease is an inherited metabolic disorder characterized by overproduction of uric acid and neurobehavioral abnormalities. The purpose of this study was to describe macrocytic erythrocytes as another common aspect of the phenotype. Methods: The results of 257 complete blood counts from 65 patients over a 23-year period were collected from 2 reference centers where many patients are seen regularly. Results: Macrocytic erythrocytes occurred in 81-92% of subjects with Lesch-Nyhan disease or its neurological variants. After excluding cases with iron deficiency because it might pseudonormalize erythrocyte volumes, macrocytosis occurred in 97% of subjects. Macrocytic erythrocytes were sometimes accompanied by mild anemia, and rarely by severe anemia. Conclusion: These results establish macrocytic erythrocytes as a very common aspect of the clinical phenotype of Lesch-Nyhan disease and its neurological variants. Macrocytosis is so characteristic that its absence should prompt suspicion of a secondary process, such as iron deficiency. Because macrocytosis is uncommon in unaffected children, it can also be used as a clue for early diagnosis in children with neurodevelopmental delay. Better recognition of this characteristic feature of the disorder will also help to prevent unnecessary diagnostic testing and unnecessary attempts to treat it with folate or B12 supplements.Wo

A new Turkish family with homozygous FBX07 truncating mutation and juvenile atypical parkinsonism

Juvenile parkinsonism can be caused by recessive mutations in several genes. Among these, homozygous or compound heterozygous mutations in the F-box only protein 7 gene (FBXO7) cause juvenile parkinsonism with variable degrees of pyramidal disturbances (PARK15). So far, only five families (from Iran, Italy, The Netherlands, Pakistan, and Turkey) have been reported with this form. Here, we describe a new Turkish family with homozygous FBXO7 mutation (c.1492C > T, p.Arg498*). Three out of nine siblings born from consanguineous parents suffered from juvenile-onset progressive parkinsonism. Mental retardation was also documented in two of them. Of note, pyramidal signs were absent. The response to dopaminergic medications was present, but limited by dyskinesias and psychiatric side effects. Further genetic analysis of this Turkish family and the Italian PARK15 family reported previously revealed that the c.1492C > T mutation is present on two different haplotypes in the Italian family, and one of these haplotypes is shared in homozygous state in the Turkish patients. These findings contribute to the ongoing delineation of the genetic and clinical spectrum of PARK15