[Early-onset familial Alzheimer's disease with spastic paraparesis associated with PSEN1 gene]. / Rannyaya semeinaya bolezn' Al'tsgeimera so spasticheskim paraparezom, svyazannaya s genom PSEN1.

A familial case of a rare autosomal dominant Alzheimer's disease (AD), related to PSEN1 gene (AD3, OMIM 607822), differing from common multifactorial form by earlier onset and, in part of cases, by accompanying neurological signs, spastic paraparesis particularly, is presented. The first sign in a female proband and in her son was paraparesis manifested at the age of 29 and 21 years, respectively. Cognitive disturbances developed soon; the former diagnosis was hereditary spastic paraplegia with cognitive impairment, In the proband examined in 2008 at 33 years old the diagnosis was not established. In the son examined in 2022 at 27 years old whole-exome sequencing detected a novel PSEN1 missense mutation p.Thr421Ala. The mutation was confirmed by Sanger sequencing in him, found out in the proband (who was severely disabled by that time) and excluded in her unaffected mother. Except for different age of onset, AD3 in two patients was similar, though in whole it is variable, also in relatives. The variability and rareness of the disease hampers clinical diagnostics. Massive parallel sequencing is a most reliable diagnostic method.

Spastic paraparesis associated with advanced liver cirrhosis: a condition obscure in terms of treatment and prognosis.

Hepatic myelopathy or spastic paraparesis of liver disease is an insidious onset condition with pure motor spastic paraparesis without sensory, bladder or bowel involvement in patients with chronic liver disease, in which the neurological dysfunction cannot be explained by other causes. It is a rare, relentlessly progressive and mostly irreversible neurological complication resulting from portosystemic shunts occurring spontaneously, created surgically or due to 'functional shunting'. In some cases, no evidence of shunting is elicitable due to difficulty in locating the hidden collaterals. We report this rare case of a 33-year-old man with chronic liver disease presenting with spastic paraparesis after 11 months of resolution of an episode of hepatic encephalopathy.

Acute encephalopathy followed by delayed myelopathy: A rare presentation of organophosphate poisoning.

Organophosphorus compounds (OPC) are commonly used pesticides and suicidal ingestion is a common mode of poisoning. The manifestation of OPC poisoning and its severity depend upon the type, dose and potency of the OPC consumed. Neurological presentations are well defined clinical syndromes consisting of early, intermediate and delayed manifestations (rare), categorised on the basis of time elapsed since OPC exposure. We report a rare delayed manifestation of organophosphorus poisoning in the form of pure motor spastic paraparesis due to dorsal myelopathy. A possibility of delayed manifestations of toxicity should be considered in individuals presenting with features suggestive of myelopathy and a previous history of organophosphate exposure.

Mutations in MTHFR and POLG impaired activity of the mitochondrial respiratory chain in 46-year-old twins with spastic paraparesis.

Hereditary spastic paraplegias (HSPs) are characterized by lower extremity spasticity and weakness. HSP is often caused by mutations in SPG genes, but it may also be produced by inborn errors of metabolism. We performed next-generation sequencing of 4813 genes in one adult twin pair with HSP and severe muscular weakness occurring at the same age. We found two pathogenic compound heterozygous variants in MTHFR, including a variant not referenced in international databases, c.197C>T (p.Pro66Leu) and a known variant, c.470G>A (p.Arg157Gln), and two heterozygous pathogenic variants in POLG, c.1760C>T (p.Pro587Leu) and c.752C>T (p.Thr251Ile). MTHFR and POLG mutations were consistent with the severe muscle weakness and the metabolic changes, including hyperhomocysteinemia and decreased activity of both N(5,10)methylenetetrahydrofolate reductase (MTHFR) and complexes I and II of the mitochondrial respiratory chain. These data suggest the potential role of MTHFR and POLG mutations through consequences on mitochondrial dysfunction in the occurrence of spastic paraparesis phenotype with combined metabolic, muscular, and neurological components.

Spastic paraparesis as the first manifestation of Machado-Joseph disease: A case report and review of the literature.

Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3, is characterized by remarkable clinical heterogeneity. We present a MJD family in which variable phenotypes were noted in affected members, including one presenting predominantly with spastic paraparesis. A review of the literature revealed that MJD with the initial presentation of spastic paraparesis is more frequently observed in cases of eastern Asian origin who carry a greater CAG expansions in the ATXN3 gene. A greatly expanded allele in ATXN3 combined with an eastern Asian genetic background is associated with a phenotype of spastic paraparesis in MJD.

Eficácia e segurança da toxina botulínica no tratamento da paraparesia espástica: revisão sistemática / Efficacy and safety of botulinum toxin in the treatment of spastic paraparesis: systematic review

A paraparesia espástica é caracterizada pela perda de função total ou parcial dos membros inferiores associado ao aumento do tônus muscular velocidade-dependente. A toxina botulínica é utilizada no tratamento de diversos padrões de espasticidade, sejam em flexão, extensão ou adução. Objetivo: determinar a eficácia e segurança do bloqueio químico com toxina botulínica em pacientes com paraparesia espástica. Método: foi realizada uma revisão sistemática com busca nas bases de dados do PUBMED, MEDLINE, LILACS e SCIELO. Os critérios de inclusão foram: ensaios clínicos que utilizaram a toxina botulínica para o tratamento de pacientes com paraparesia espástica e publicados em inglês a partir da década de 1980. Os desfechos considerados foram: a pontuação na Escala de Ashworth Modificada, a amplitude de movimento passiva e ativa e os efeitos adversos da toxina botulínica. Resultados: foram incluídos cinco artigos. Todos mostraram melhora da espasticidade nos pacientes estudados. Quatro artigos mostraram aumento da amplitude de movimento passivo e três relataram aumento da amplitude de movimento ativo. Três artigos trouxeram relatos de efeitos adversos após o uso da toxina botulínica, mas a maioria deles não eram graves e cessaram espontaneamente. Conclusão: os estudos analisados mostraram que a toxina botulínica é eficaz e segura em pacientes com paraparesia espástica.(AU)

Spastic paraparesis is the loss of total or partial lower limb function associated with increased speed-dependent muscle tone. Botulinum toxin is used in the treatment of several spasticity presentations that include flexion, extension and adduction. Objective: To determine both safety and efficacy of botulinum toxin as a blocking agent in the treatment of spastic paraparesis. Method:A systematic review was carried out with a search on PUBMED, MEDLINE, LILACS and SCIELO databases. The inclusion criteria were: clinical trials that used botulinum toxin for the treatment of patients with spastic paraparesis and published in English from the 1980s. The following outcomes were assessed by the studies: the Ashworth Modified scale score, the range of passive and active motion and botulinum toxin adverse effects. Results:Five articles were included. All of them showed spasticity improvements in the patients. Four studies showed increases in passive range of motion and three articles showed increase in active range of motion. Three papers reported adverse effects after botulinum toxin use but they were mostly mild and ceased spontaneously. Conclusion: Most analyzed studies indicated that botulinum toxin is safe and efficient inthe treatment of spastic paraparesis. (AU)

Spastic paraparesis caused by X-linked adrenoleukodystrophy mimicking vacuolar myelopathy in a human immunodeficiency virus patient: A case report.

RATIONALE: Vacuolar myelopathy is one of most common cause of spastic paresis in patients with human immunodeficiency virus (HIV) infection. However, X-linked adrenoleukodystrophy (X-ALD), which is a metabolic disorder caused by impairment of peroxisomal beta-oxidation of very-long-chain fatty acids (VLCFA), also manifests as various neurological deteriorations including adult onset spastic paraparesis. To the best of our knowledge, there has been no report of newly developed spastic paresis due to X-ALD in a patient with HIV infection. PATIENT CONCERNS: A 30-year-old male had presented with progressive spastic paraparesis for 1 year. DIAGNOSIS: X-ALD. INTERVENTION: Brain and spine magnetic resonance imaging (MRI), VLCFA, and genetic test. OUTCOMES: His spinal MRI mimicked vacuolar myelopathy, but he was finally diagnosed with X-ALD using the VLCFA and genetic test. LESSONS: Although rare, isolated spastic paraparesis can occur in HIV patients; additional tests such as VLCFA can be useful for the differential diagnosis. More data are needed to understand the pathological mechanisms underlying the two diseases.

Personalized upper limb training combined with anodal-tDCS for sensorimotor recovery in spastic hemiparesis: study protocol for a randomized controlled trial.

BACKGROUND: Recovery of voluntary movement is a main rehabilitation goal. Efforts to identify effective upper limb (UL) interventions after stroke have been unsatisfactory. This study includes personalized impairment-based UL reaching training in virtual reality (VR) combined with non-invasive brain stimulation to enhance motor learning. The approach is guided by limiting reaching training to the angular zone in which active control is preserved ("active control zone") after identification of a "spasticity zone". Anodal transcranial direct current stimulation (a-tDCS) is used to facilitate activation of the affected hemisphere and enhance inter-hemispheric balance. The purpose of the study is to investigate the effectiveness of personalized reaching training, with and without a-tDCS, to increase the range of active elbow control and improve UL function. METHODS: This single-blind randomized controlled trial will take place at four academic rehabilitation centers in Canada, India and Israel. The intervention involves 10 days of personalized VR reaching training with both groups receiving the same intensity of treatment. Participants with sub-acute stroke aged 25 to 80 years with elbow spasticity will be randomized to one of three groups: personalized training (reaching within individually determined active control zones) with a-tDCS (group 1) or sham-tDCS (group 2), or non-personalized training (reaching regardless of active control zones) with a-tDCS (group 3). A baseline assessment will be performed at randomization and two follow-up assessments will occur at the end of the intervention and at 1 month post intervention. Main outcomes are elbow-flexor spatial threshold and ratio of spasticity zone to full elbow-extension range. Secondary outcomes include the Modified Ashworth Scale, Fugl-Meyer Assessment, Streamlined Wolf Motor Function Test and UL kinematics during a standardized reach-to-grasp task. DISCUSSION: This study will provide evidence on the effectiveness of personalized treatment on spasticity and UL motor ability and feasibility of using low-cost interventions in low-to-middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02725853 . Initially registered on 12 January 2016.

A comprehensive person-centered approach to adult spastic paresis: a consensus-based framework.

Spastic paresis is a common feature of an upper motor neuron impairment caused by stroke, brain injury, multiple sclerosis and other central nervous system (CNS) disorders. Existing national and international guidelines for the treatment of adult spastic paresis tend to focus on the treatment of muscle overactivity rather than the comprehensive approach to care, which may require life-long management. Person-centered care is increasingly adopted by healthcare systems in a shift of focus from "disease-oriented" towards "person-centered" medicine. The challenge is to apply this principle to the complex management of spastic paresis and to include an educative process that engages care providers and patients and encourages them to participate actively in the long-term management of their own disease. To address this issue, a group of 13 international clinicians and researchers used a pragmatic top-down methodology to evaluate the evidence and to formulate and grade the strength of recommendations for applying the principles of person-centered care to the management of spastic paresis. There is a distinct lack of clinical trial evidence regarding the application of person-centered medicine to the rehabilitation setting. However, the current evidence base supports the need to ensure that treatment interventions for spastic paresis should be centered on as far as reasonable on the patient's own priorities for treatment. Goal setting, negotiation and formal recording of agreed SMART goals should be an integral part of all spasticity management programs, and goal attainment scaling should be recorded alongside other standardized measures in the evaluation of outcome. When planning interventions for spastic paresis, the team should consider the patient and their family's capacity for self-rehabilitation, as well as ways to enhance this approach. Finally, the proposed intervention and treatment goals should consider the impact of any neuropsychological, cognitive and behavioral deficits on rehabilitation. These recommendations support a person-centric focus in the management of spastic paresis.

A Middle-aged Man With Progressive Ophthalmoparesis, Ataxia, and Spastic Paraparesis.

A 50-year old man presented for evaluation of progressive gait ataxia with a superimposed spastic paraparesis. During his clinic visit, he was also observed to have slow and limited eye movements. In this article, we discuss the clinical approach to this triad of symptoms and guide the reader to discover the patient's ultimate genetic diagnosis.

Episodic spastic paraparesis successfully treated with unaided blood transfusions: a case report.

BACKGROUND: Extramedullary haemopoiesis is a common compensatory phenomenon in most haemolytic anaemias. However, spinal cord compression due to extramedullary spinal epidural haemopoiesis is an extremely rare complication of thalassemia. In such situation patients present with paraplegia with a sensory level. Usual treatment options are surgery and/or radiotherapy. CASE PRESENTATION: Here we report a 27 year old Sri Lankan Muslim male with haemoglobin E-Beta thalassaemia presented with episodic spastic paraparesis when he was anaemic which was dramatically responded to blood transfusion therapy. CONCLUSION: Most of the reported cases with paraplegia have been treated with surgery with or without radiation therapy or radiation therapy alone. Our patient makes dramatic recovery after blood transfusion in each presentation.

Neurology assessment by objective structured video examination.

BACKGROUND: The ability to carry out a neurological examination and make an appropriate differential diagnosis is one of the mainstays of our final Bachelor of Medicine (MB) exam; however, with the introduction of objective structured clinical examinations (OSCEs) it has become impossible to arrange for adequate numbers of suitable real patients to participate in the exam. CONTEXT: It is vital that newly qualified doctors can perform a basic neurological examination, interpret the physical signs and formulate a differential diagnosis. It is vital that newly qualified doctors can perform a basic neurological examination INNOVATION: Since 2010 we have introduced an objective structured video examination (OSVE) of a neurological examination of a real patient as part of our final MB OSCE exam. The students view clips of parts of the examination process. They answer questions on the signs that are demonstrated and formulate a differential diagnosis. IMPLICATIONS: This type of station is logistically a lot easier to organise than a large number of real patients at different examination sites. The featured patients have clearly demonstrated signs and, as every student sees the same patient, are perfectly standardised. It is highly acceptable to examiners and performed well as an assessment tool. There are, however, certain drawbacks in that we are not examining the student's examination technique or their interaction with the patient. Also, certain signs, in particular the assessment of muscle tone and power, are more difficult for a student to estimate in this situation.

Paraparesia espástica progresiva y siringomielia estática: síndrome de Silver/SPG17 / Progressive spastic paraparesis and static syringomyelia: Silver syndrome/SPG17

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The difficulty in diagnosing X linked adrenoleucodystrophy and the importance of identifying cerebral involvement.

Two patients are described, a mother and son, who were initially clinically diagnosed with hereditary spastic paraparesis. This was rectified after very long chain fatty acid testing confirmed adrenomyeloneuropathy (AMN). The son's initial symptoms were characteristic of AMN (the commonest phenotype) but progressed to show symptoms of cerebral involvement. This evolution from non-cerebral to cerebral AMN is recognised in the medical literature and is increasingly important to consider in light of the availability of potential treatments such as haematopoietic stem cell transplantation.

Atypical presentation of CLIPPERS syndrome: a new entity in the differential diagnosis of central nervous system rheumatologic diseases.

Numerous autoimmune diseases can affect the central nervous system (CNS), and variable clinical presentations confound the differential diagnosis. The challenging task of properly characterizing various CNS autoimmune diseases enables patients to be rapidly triaged and appropriately treated. In this review article, we aim to explore different CNS manifestations of rheumatologic diseases with emphasis on the utility of imaging and cerebrospinal fluid findings. We review the classic physical examination findings, characteristic imaging features, cerebrospinal fluid results, and serum biomarkers. In addition, we also present a unique case of newly described autoimmune entity CLIPPERS syndrome. Our case is unique in that this is the first case which demonstrates involvement of the supratentorial perivascular spaces in addition to the classic infratentorial involvement as initially described by Pittock et al (Brain. 2010;133:2626-2634).