Pyramidal Syndrome Research Articles

Results of tonic and burst epidural spinal cord stimulation in patients with spasticity, chronic disorders of consciousness and neuropathic pain syndrome at the rehabilitation stage

The paper analyzes the experience of using epidural spinal cord stimulation in tonic and burst stimulation modes in 71 patients with the consequences of damage to the central nervous system, who underwent treatment and rehabilitation at the Research Institute of Rehabilitology named after professor I.V. Pryanikov, FSCC RR, from 2020 to 2021. The efficacy of epidural stimulation in the indicated modes for clinical manifestations of pyramidal syndrome in the extremities, chronic disorders of consciousness, neuropathic pain, and paresis of the extremities without spasticity has been studied. The use of invasive spinal cord stimulation in the burst mode in patients with spasticity and chronic disorders of consciousness is described for the first time. The impact of various factors on the effectiveness of stimulation has also been analyzed. The average age of patients in the study group was 47 ± 17 years, the average duration of test epidural stimulation was 4.3 ± 1.6 days. Twenty-eight patients (39.5%) were stimulated in the tonic mode, twenty-two patients (31%) were stimulated in the burst mode, and the remaining patients were stimulated in the combined mode. Results: positive dynamics after the use of epidural stimulation was observed in 39 patients (54.9%). The spasticity regressed in 32 patients (52.5%); in addition, an increase in the active range of motion was observed in 23 patients (37.7%) from this subgroup. The decrease in the severity of spasticity in the extremities ranged from 0.33 ± 0.1 to 0.63 ± 0.13 points (p<0.005). The signs of an increase in the level of consciousness as a result of the stimulation were noted in 8 patients (38.1%); the neuropathic pain syndrome regressed in 8 patients (72.7%). When applying this technique in patients with paresis without spasticity, the stimulation did not have an effect in any patients of this subgroup. There was no statistically significant influence of etiology, age of patients or duration of stimulation on its effect. The patients with spasticity, who were stimulated in the tonic mode, more often demonstrated the effectiveness of stimulation compared with the patients from the combined mode subgroup (p<0.013). Higher effectiveness of the burst mode stimulation compared to the combined mode stimulation in patients with spasticity was on the borderline of statistical significance (p=0.065). Thus, the use of epidural stimulation in patients with chronic neuropathic pain and spasticity showed the best results; the effect of epidural stimulation on the level of consciousness in chronic disorders requires additional studies and changes in their design.

GAMBARAN KEJADIAN EKSTRAPIRAMIDAL SINDROM PADA PASIEN TERAPI ANTIPSIKOTIK TIPIKAL DI RUMAH SAKIT JIWA ACEH

The use of antipsychotics in schizophrenic patients often causes side effects in the form of Extra Pyramidal Syndrome (EPS), namely the presence of uncontrolled muscle movement disorders such as seizures, shaking and so on. The incidence of EPS is more common with the use of typical antipsychotics than atypicals. This study aims to see the incidence of EPS in inpatients with schizophrenia at the Aceh Mental Hospital located in Banda Aceh in 2020. The population in this study were all inpatients who were given typical antipsychotics. While the research sample was 399 samples collected from medical record data of inpatients in 2020, so the study was retrospective with a cross sectional approach. Data collected in the form of patient identity (gender, age), drug therapy (typical antipsychotics) and the incidence of EPS. The results showed that schizophrenic patients who received typical antipsychotic therapy who were hospitalized at the Aceh mental hospital in 2020, were 324 men (81.2%) and 75 women (18.8%), with the highest age range being at 36-45 years amounting to 202 people (50.6%). Typical antipsychotic therapy used in the form of combination of typical-typical and typical-atypical drugs, namely clozapine-trifluperazine (40.6%), chlorpromazine-risperidone (20.3%), haloperidol-chlorpromazine-trifluperazine (16%), haloperidolchlorpromazine (7%), and haloperidol-trifluperazine (5%). The incidence of EPS that occurred was 113 people (28.3%), with the highest number of EPS occurring from the administration of haloperidol-chlorpromazine-trifluperazine combination antipsychotic therapy, which was 61 people (15.3%).

Clinical, phenotypic and genetic landscape of case reports with genetically proven inherited disorders of vitamin B12 metabolism: A meta-analysis

SummaryInherited disorders of B12 metabolism produce a broad spectrum of manifestations, with limited knowledge of the influence of age and the function of related genes. We report a meta-analysis on 824 patients with a genetically proven diagnosis of an inherited disorder of vitamin B12 metabolism. Gene clusters and age categories are associated with patients’ manifestations. The “cytoplasmic transport” cluster is associated with neurological and ophthalmological manifestations, the “mitochondrion” cluster with hypotonia, acute metabolic decompensation, and death, and the “B12 availability” and “remethylation” clusters with anemia and cytopenia. Hypotonia, EEG abnormalities, nystagmus, and strabismus are predominant in the younger patients, while neurological manifestations, such as walking difficulties, peripheral neuropathy, pyramidal syndrome, cerebral atrophy, psychiatric disorders, and thromboembolic manifestations, are predominant in the older patients. These results should prompt systematic checking of markers of vitamin B12 status, including homocysteine and methylmalonic acid, when usual causes of these manifestations are discarded in adult patients.

Novel SEPSECS Pathogenic Variants Featuring Unusual Phenotype of Complex Movement Disorder With Thin Corpus Callosum: A Case Report.

ObjectivesTo report a novel association between pathogenic variants in the SEPSECS gene and complex movement disorder with thin corpus callosum (TCC).MethodsClinical exome sequencing was performed in an adult patient with a genetically unsolved neurodegenerative disorder. The main clinical, neuroimaging, and genetic data were described.ResultsThe c.865C > T (p.P289S) and c.1297T > C (p.Y433H) missense variants in SEPSECS (NM_016,955.3) were discovered.DiscussionThis case represents a novel form of early-onset pyramidal syndrome with optic nerve hypoplasia, which slowly evolved to extrapyramidal syndrome featuring dystonia-parkinsonism, associated with TCC, caused by SEPSECS pathogenic variants. This form enlarges the group of the so-called pyramidal-extrapyramidal syndromes, as well as complex hereditary spastic paraparesis with TCC.

Subacute Chorea Induced by Organic Solvents

Introduction: Chronic exposure to organic solvents may result in a variety of neurologic complications like dementia, cerebellar dysfunction, pyramidal syndrome, cranial nerve abnormalities, and neuropathy. Clinical Presentation: We report an unusual case of subacute chorea induced by occupational exposure. Brain magnetic resonance imaging showed diffuse white matter T2 hyperintensity. The screening of basic blood tests, and CSF studies to eliminate alternate diagnoses, were normal. The patient received 1000 mg/day of intravenous methylprednisolone for 3 days, with cessation of professional activity. We observed a regression of neurological symptoms after 3 months of follow-up. Conclusion: This case highlights the diversity of acute or chronic neurological complications of solvents.

Secondary neurogenic prosopalgia in a neurological clinic

Annotation. Prosoplgia is one of the most common pain syndromes in the craniofacial area. In the clinic practice of the facial pain treatment, neurogenic prosopalgia accounts for 25-30% of cases. The aim of the study was to evaluate the clinical, laboratory and functional parameters of patients with secondary neurogenic prosopalgia at neurological department. The medical histories of 21 patients (17 (81.0%) women and 4 (19.0%) men) suffered from secondary neurogenic prosopalgia were analyzed retrospectively. The clinical picture, data of general blood and urine tests, biochemical blood tests, neuroimaging, electrophysiological and ultrasonic research methods were evaluated. A preliminary comparison of retrospective patients quality indicators was assessed using simple mathematical methods. A predominant lesion of the I branch of the trigeminal nerve was shown in elderly women with postherpetic neuralgia, while other reasons of secondary neuralgia of the II and III branches of the trigeminal nerve more often caused left-sided lesions. Primary diseases included: herpetic ganglionitis, malignant tumor of the bladder with herpetic complications, sinusitis, dental diseases, meningoencephalitis, atherosclerosis of the brain vessels, concussion of the brain. The features of the clinical picture of each case were evaluated, as well as the characteristic concomitant groups of symptoms, among which were determined cephalgic, asthenoneurotic, vestibulo-atactic, vegetative dystonia, pyramidal syndromes. Among the general and functional studies carries out, attention was drawn to the increase of ESR in almost half of the patients, even without exacerbation of the primary disease, as well as the presence of metabolic disorders in the myocardium according to the electrocardiogram in 47.6% of cases, including in relatively young individuals. Thus, the problem of secondary neurogenic prosopalgia, despite the modern treatment, remains relevant.

Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview.

Hereditary spastic paraplegias (HSP) are a heterogeneous group of motor neurodegenerative disorders that have the core clinical presentation of pyramidal syndrome which starts typically in the lower limbs. They can present as pure or complex forms with all classical modes of monogenic inheritance reported. To date, there are more than 100 loci/88 spastic paraplegia genes (SPG) involved in the pathogenesis of HSP. New patterns of inheritance are being increasingly identified in this era of huge advances in genetic and functional studies. A wide range of clinical symptoms and signs are now reported to complicate HSP with increasing overall complexity of the clinical presentations considered as HSP. This is especially true with the emergence of multiple HSP phenotypes that are situated in the borderline zone with other neurogenetic disorders. The genetic diagnostic approaches and the utilized techniques leave a diagnostic gap of 25% in the best studies. In this review, we summarize the known types of HSP with special focus on those in which spasticity is the principal clinical phenotype (“SPGn” designation). We discuss their modes of inheritance, clinical phenotypes, underlying genetics, and molecular pathways, providing some observations about therapeutic opportunities gained from animal models and functional studies. This review may pave the way for more analytic approaches that take into consideration the overall picture of HSP. It will shed light on subtle associations that can explain the occurrence of the disease and allow a better understanding of its observed variations. This should help in the identification of future biomarkers, predictors of disease onset and progression, and treatments for both better functional outcomes and quality of life.

Pattern of Brain Injury in Patients With Thrombotic Thrombocytopenic Purpura in the Precaplacizumab Era.

To describe short- and long-term neurologic prognosis of patients with thrombotic thrombocytopenic purpura and to identify clusters associated with evolution. Prospective French cohort. ICU in a reference center. All consecutive patients with newly diagnosed thrombocytopenic purpura. Comprehensive clinical, biological, and radiological evaluation at admission. Neurocognitive recovery was assessed using Glasgow Outcome Scale (range 1-5, with 1 representing death and 5 representing no or minimal neurologic deficit). Among the 130 newly diagnosed patients with thrombocytopenic purpura, 108 (83%; age 43 [30-52]; 73% women) presented with neurologic signs, including headaches (51%), limb weakness, paresthesia, and/or aphasia (49%), pyramidal syndrome (30%), decreased consciousness (20%), seizure (19%), cognitive impairment (34%), cerebellar syndrome (18%), and visual symptoms (20%). A hierarchical cluster analysis identified three distinct groups of patients. Cluster 1 included younger patients (37 [27-48], 41 [32-52], and 48 [35-54], in clusters 1, 2 and 3, respectively; p = 0.045), with a predominance of headaches (75%, 27%, and 36%; p < 0.0001). Cluster 2 patients had ataxic gait and cerebellar syndrome (77%, 0%, and 0%; p < 0.0001) and dizziness (50%, 0%, and 0%; p < 0.0001). Cluster 3 included patients with delirium (36%, 0%, and 9%; p < 0.0001), obtundation (58%, 0%, and 24%; p < 0.0001), and seizure (36%, 0%, and 14%; p < 0.0001). Acute kidney injury was 32%, 68%, and 77%, in clusters 1, 2, and 3, respectively (p < 0.0001). The three clusters did not differ for other biological or brain imaging. After a median follow-up of 34 months (12-71 mo), 100 patients (93%) were alive with full neurocognitive recovery (i.e., Glasgow Outcome Scale score 5) in 89 patients (89%). Patients from cluster 1 more frequently exhibited full recovery (Glasgow Outcome Scale score of 5) compared with clusters 2 and 3, (44 [98%], 13 [65%], and 21 [60%] at 3 mo; p < 0.0001), (44 [100%], 15 [68%], and 23 [69%] at 6 mo; p < 0.0001), and (40 [100%], 15 [79%], and 20 [57%] at 1 yr; p < 0.0001). Initial clinical neurologic evaluation in thrombocytopenic purpura patients distinguishes three groups of patients with different clinical and functional outcomes.

MO232BORTEZOMIB INDUCED PERIPHERAL AND CENTRAL NEUROPATHY : ABOUT 3 CASE REPORTS

Abstract Background and Aims Bortezomib is a proteasome inhibitor, whose efficacy in the treatment of multiple myeloma has been proven over the last years. However, its side effects may cause concern for patients as well as physicians. We focused in this study on Bortezomib-induced neuropathy, one of the most frequent complications. We present 2 cases of peripheral sensory neuropathy and one intriguing case of central neurological manifestation, all caused by Bortezomib administration. Case 1 A 62-year-old man, with a history of diabetes and hypertension, was diagnosed with multiple myeloma in 2019. He received 2 cycles of Bortezamib (2,5 mg), Dexamethasone , and Cyclophosphamide. Each cycle included 4 doses of Bortezomib, and the cycles were 21 days apart. At the end of the second cycle the patient developed posterior cord syndrome with balance disorder and lower extremities paresthesia. Axonal sensitivo-motor polyneuropathy was confirmed by electromyography. A pharmacology investigation was conducted, and the symptoms were attributed to Bortezomib toxicity. Evolution was favourable after change in protocol to Revlimide. No recurrence was noted. Case 2 A 64-year-old man with no prior history was diagnosed with multiple myeloma in 2020. She received a protocol of 4 cycles, 21 days apart, of Bortezomib (2.1 mg) ,Dexamethasone and Thalidomide . Three weeks after the first cycle, the patient presented with confusion, gait disturbance and four-limb pyramidal deficiency syndrome. Electromyography showed axonal sensitivo-motor polyneuropathy .In the absence of other causes, Bortezomib toxicity was suspected and the patient underwent an emergency epurative hemodialysis session, after which symptoms completely disappeared. Bortezomib doses were then reduced. The evolution was favourable. Case 3 A 50-year-old woman was diagnosed with multiple myeloma in 2018 with Randall's disease and quadri-pyramidal syndrome. She was put on 4 courses of Bortezomib 2.4mg Cyclophosphamide and Dexamethasone, 21 days apart. After 2 coursess, she presented a generalized tonic-clonic seizure preceded by headache, dizziness and followed by speech disturbances. Biological screening for metabolic disorders and toxins was unremarkable. Cerebral MRI showed no abnormalities. Doses of Bortezomib were reduced during the following course. We then witnessed an improvement in speech and no recurrence of seizures. Conclusion Bortezomib induced neuropathy is a serious and debilitating complication to which physicians must pay special attention. This side effect can be managed by dose reduction or change of molecules. Outcomes are often favourable.

Neurological symptoms in spinal syndromes

Spinal cord injuries are frequently associated with severe clinical-neurological deficits. These are evident with specific symptoms and syndromes. Hereby, athorough knowledge of spinal neuroanatomy is essential. Spinal anatomy, examination procedures and classical spinal syndromes are presented. Important spinal syndromes comprise the dorsal cord syndrome, spinothalamic tract syndrome, pyramidal tract syndrome, central cord syndrome, transversal and Brown-Séquard syndrome as well as combined syndromes. Clinical examination allows assessment and anatomical classification of spinal syndromes and targeted examination of the spinal cord using additional diagnostic methods.

Clinical and Nutritional Evolution of 24 Patients with Glutaric Aciduria Type 1 in Follow-up at a Center Specialized in Inborn Errors of Metabolism in Chile

Introduction: Glutaric Aciduria Type 1 (GA-1) is produced by the enzymatic deficiency of glutaryl-CoA-dehydrogenase (GCDH), leading to the accumulation of glutaric acid (GA). 90% of patients without early treatment present acute encephalopathic crisis (AEC), followed by disabling neurological symptoms. The treatment consists of a low lysine (Lys) diet, protein substitute lys-free, tryptophan-reduced (PS) and L-carnitine. Objectives: Describe the clinical and nutritional evolution of a cohort of GA-1 patients at a national referral center in Chile. Methodology: Retrospective study of 24 patients diagnosed with GA-1 between 1998-2020 and referred to the Institute of Nutrition and Food Technology (INTA) of University of Chile. Results: Age at diagnosis was 19±27 months; 10/24 presented AEC and neurological sequelae. The cases without AEC (14/24) 8 presented neurological compromise: psychomotor development delay, abnormal movements and pyramidal syndrome. Nutritional evaluation: 12/24 were malnourished by deficiency, <6 years old group (12/24): 11 cases were found to have Lys and PS, ≥6 years old (12/24): 9/12 did not receive PS. All had normal free carnitine levels. Conclusion: GA-1 has variable symptoms with neurological involvement AEC or insidious start. Is essential to maintain a long-term follow-up and consider its inclusion in neonatal screening programs.

Hemorrhagic Stroke: About a Pediatric Case

Stroke is a rare but serious condition with high mortality and morbidity. We report the case of a 10-year-old child with no known pathological history who was transferred to the pediatric department for hemorrhagic stroke. He had been hospitalized 6 days earlier in a peripheral center for a tonic-clonic seizure accompanied by loss of consciousness and fever. Clinical examination revealed meningeal syndrome, facial paralysis, right hemiparesis, ataxia with disturbed balance, aphasia, and a peripapillary hemorrhage on the fundus. A cerebral computed tomography (CT) scan showed a hemorrhagic stroke with ventricular flooding. A lumbar puncture was performed and a hematic cerebrospinal fluid (CSF) with 12 leukocytes and 8000 red blood cells was obtained. The evolution was marked by the extinction of the infectious and meningeal syndromes, the regression of the pyramidal syndrome and the persistence of the dysarthria justifying a neuropsychological and speech therapy follow-up. Several challenges (diagnostic, therapeutic) exist in the management of children with stroke. Prospective studies with a larger sample are needed to fill the observed gaps.

A Study of Metabolic Syndrome in Patients on Risperidone

Background: Novel antipsychotics are superior to conventional antipsychotics, as they significantly reduce both positive and negative symptoms of schizophrenia and have lower risk of extra pyramidal syndrome (EPS). However, these drugs cause significant metabolic side effects. Objective: This study was carried out to assess the hospital prevalence of metabolic syndrome (MetS) and metabolic profile related to use of oral risperidone which is one of the most commonly used atypical antipsychotics. Methods: A cross-sectional study was carried out on a period sample of 6 months, to study the hospital prevalence and profile of MetS in adult patients on oral risperidone. Data was collected from pharmacy dispensing records, patients’ case record files, and subsequently patients were contacted telephonically and called to participate in this study. Results: Hospital prevalence of MetS was found to be 12.1% (13 out of 107) by NCEP ATP III criteria and 14.9% (16 out of 107) by IDF criteria in patients (aged 20 to 40 years) on risperidone. Ninety one patients (85%) of the sample were found to be in Overweight category and Central Obesity was found in 82(76.6%) patients. Twenty three (21.4%) of the patients had increased triglyceride (TG) levels. Out of the 16 patients with MetS, 11(68.75%) of them had total duration of illness (TDI) of &gt;4 years, 11(68.75%) were in 30-40 years age group, 13 (81.25%) of them had continued illness or they were in partial remission, 11 (68.75%) of them were already exposed to any antipsychotics other than risperidone, 6(37.5%) of them were having diabetes mellitus (DM) in one parents. Conclusion: This study reported the hospital prevalence of MetS as 14.9% (IDF criteria) in young adult patients on oral risperidone. The triglyceride levels and central obesity was also found to be higher in patients, who otherwise had low prevalence of MetS.

Phase I trial of D2C7 immunotoxin (D2C7-IT) administered intratumorally via convection-enhanced delivery (CED) for recurrent malignant glioma (MG).

2566 Background: D2C7-IT is a recombinant immunotoxin comprised of a dual-specific antibody fragment targeting EGFRwt and EGFRvIII and a genetically engineered form of the Pseudomonas exotoxin, PE38-KDEL. We report the results of a phase I trial evaluating D2C7-IT delivered intratumorally by CED. Methods: Eligible patients were adults with recurrent supratentorial WHO grade III or IV MG; solitary tumor; ≥4 weeks after chemotherapy, bevacizumab or study drug; adequate organ function; and KPS&gt;70%. Two patients per dose level (DL) were to enroll in the dose escalation portion (dose range: 40ng/mL to 23,354ng/mL). Results: From May 2015 to May 2018, 43 patients enrolled on study. Observed dose limiting toxicities include: grade 4 seizure (n=1) on DL3, grade 3 confusion and pyramidal tract syndrome (n=1) on DL13, and grade 4 cerebral edema (n=1) and grade 3 dysphasia (n=1) on DL17. Grade 3 or higher adverse events possibly related to D2C7-IT include: seizure (grade 4, n=2; grade 3, n=3), cerebral edema (grade 4, n=1), hydrocephalus (grade 3, n=5), headache (grade 3, n=4), hemiparesis (grade 3, n=4), dysphasia (grade 3, n=3), lymphopenia (grade 3, n=4), thromboembolic event (grade 3, n=3); and one each of grade 3 elevated ALT, urinary tract infection, fall, wound complication, generalized muscle weakness, confusion, encephalopathy, and somnolence. As of February 2020, four patients remain alive, with three patients demonstrating persistent radiographic partial response more than 54, 34 and 28 months after a single infusion of D2C7-IT. Conclusions: Dose level 13 (6,920ng/mL) was selected as the optimal phase II dose. Accrual in a dose expansion phase II trial is ongoing, and we are initiating a combination trial of D2C7-IT with checkpoint inhibitior. Clinical trial information: NCT02303678 .

A complete overview of REEP1: old and new insights on its role in hereditary spastic paraplegia and neurodegeneration.

At the end of 19th century, Adolf von Strümpell and Sigmund Freud independently described the symptoms of a new pathology now known as hereditary spastic paraplegia (HSP). HSP is part of the group of genetic neurodegenerative diseases usually associated with slow progressive pyramidal syndrome, spasticity, weakness of the lower limbs, and distal-end degeneration of motor neuron long axons. Patients are typically characterized by gait symptoms (with or without other neurological disorders), which can appear both in young and adult ages depending on the different HSP forms. The disease prevalence is at 1.3-9.6 in 100 000 individuals in different areas of the world, making HSP part of the group of rare neurodegenerative diseases. Thus far, there are no specific clinical and paraclinical tests, and DNA analysis is still the only strategy to obtain a certain diagnosis. For these reasons, it is mandatory to extend the knowledge on genetic causes, pathology mechanism, and disease progression to give clinicians more tools to obtain early diagnosis, better therapeutic strategies, and examination tests. This review gives an overview of HSP pathologies and general insights to a specific HSP subtype called spastic paraplegia 31 (SPG31), which rises after mutation of REEP1 gene. In fact, recent findings discovered an interesting endoplasmic reticulum antistress function of REEP1 and a role of this protein in preventing τ accumulation in animal models. For this reason, this work tries to elucidate the main aspects of REEP1, which are described in the literature, to better understand its role in SPG31 HSP and other pathologies.

THE COMPREHENSIVE EVALUATION OF PATIENTS’ CONDITION IN RECOVERY AND RESIDUAL PERIODS OF ANEURYSMAL SUBARACHNOID HEMORRHAGE

The aim: is to evaluate peculiarities of clinical and neurological characteristics, quality of life, brain morphometry changes and metabolic deviations of patients, who suffered from aneurysmal subarachnoid hemorrhage. Materials and methods: In the period of 2016-2019 we examined 114 patients, who signed the informed consent, taking into account their age, clinical and anatomical form of hemorrhage, disease duration, Hunt-Hess severity grade, complications of acute period. Such parameters were evaluated, as clinical and neurological characteristics, the degree of the Barthel index and the modified Rankin scale, cognitive functioning (MoCA), psycho-emotional sphere and quality of life (HADS, SF-36), morphometric parameters based on brain computed tomography measurements, explored the indicators of apoptosis, mitochondrial dysfunction, intracellular oxidative stress. Results: Сephalgia (90,35 %), pyramidal syndrome (53,50 %), sensibility deficit (36,84 %) were leading among the all neurological syndromes. Slight dependence and disability grade was found during assessment of the Barthel index and the modified Rankin scale. In 85,96 % of patiens we revealed cognitive impairment of different severity grades. The anxiety was manifested in 65,79 %, depression - in 64,91 % of patients. Due to the morphometry data, the process of cerebral atrophy was detected (central - in 26,31 % of patients, cortical - in 16,67% and mixed - in 28,07 %). AnV+ and PI+ - cells level exceeded normal values in 2,88 and 1,96 times while the level of JC-1+ and ROS+-cells - in 2,17 and 2,82 times (p<0,01). Conclusions: Having studied clinical and neurological, neuropsychological, morphometric and metabolic factors, we found their pathogenetic role in the course of late recovery and residual periods of aneurysmal subarachnoid hemorrhage, that would help us to improve the diagnostic tactics and reveal the predictors of unfavorable outcome.

The effect of stretching exercises as part of the rehabilitation program for patients with spinal cord injury

Introduction &amp; objectives: Spinal cord injury is a neurological condition with a devastating impact on all aspects of patients’ life. Spasticity, a symptom of the resulting pyramidal syndrome, can be both beneficial and non-beneficial, and requires treatment when it causes significant limitations and complications. The therapeutic approach comprises a wide variety of therapies ranging from non-invasive to invasive procedures. One of the non-invasive procedures is physiotherapy including stretching exercises. There are several studies investigating the effects of stretching on spasticity but with inconclusive results, slightly favoring a positive effect. The aim of this case-control study was to evaluate the effect of a stretching module added to the specific physiotherapy program for patients with SCI. Material and method: An observational case-control study was conducted which included 20 patients with SCI attending a motor neurorehabilitation program for 10 consecutive days at the Rehabilitation Hospital Cluj-Napoca and “Dorina Palace” Center, Cluj-Napoca, during the years 2016-2017. The patients were divided into 2 groups of 10 patients each: the control group, which received specific physiotherapy and occupational therapy, and the study group, in which a stretching exercise module was added to the rehabilitation program (attended by the control group). The patients were assessed using the Modified Ashworth Scale, the Range of Motion (ROM) test for the lower limb joints, and the Ten Meter Walk Test, both at the beginning and at the end of the 10-days rehabilitation program. Results &amp; discussions: The patients in the study group had statistically significant improvements in all the assessed scores compared to the control group, in which improvements were also present, but at the limit of statistical significance. Conclusion: The inclusion of stretching exercises in the specific physiotherapy program for patients with spastic paraparesis after spinal cord injury seems to have a short-term favorable impact, by reducing spasticity and improving ambulation. Key words: spinal cord injury, spasticity, stretching,

Long-term follow-up until early adulthood in autosomal dominant, complex SPG30 with a novel KIF1A variant: a case report

BackgroundPathogenic variants in KIF1A (kinesin family member 1A) gene have been associated with hereditary spastic paraplegia (HSP) type 30 (SPG30), encopassing autosomal dominant and recessive, pure and complicated forms.Case presentationWe report the long-term follow-up of a 19 years-old boy first evaluated at 18 months of age because of toe walking and unstable gait with frequent falls. He developed speech delay, mild intellectual disability, a slowly progressive pyramidal syndrome, microcephaly, bilateral optic subatrophy and a sensory axonal polyneuropathy. Brain MRI showed cerebellar atrophy, stable along serial evaluations (last performed at 18 years of age). Targeted NGS sequencing disclosed the de novo c.914C > T missense, likely pathogenic variant on KIF1A gene.ConclusionsWe report on a previously unpublished de novo heterozygous likely pathogenic KIF1A variant associated with slowly progressive complicated SPG30 and stable cerebellar atrophy on long-term follow-up, adding to current knowledge on this HSP subtype.

ATIM-24. DOSE FINDING AND DOSE EXPANSION TRIAL OF D2C7 IMMUNOTOXIN (D2C7-IT) ADMINISTERED INTRATUMORALLY VIA CONVECTION-ENHANCED DELIVERY (CED) FOR RECURRENT MALIGNANT GLIOMA (MG)

Abstract BACKGROUND D2C7-IT is a recombinant immunotoxin comprised of a dual-specific antibody fragment targeting EGFRwt and EGFRvIII and a genetically engineered form of the Pseudomonas exotoxin, PE38-KDEL. We report results of a phase 1 trial, with dose expansion at the selected phase 2 dose, evaluating D2C7-IT delivered intratumorally by CED. METHODS Eligible patients are adults with recurrent supratentorial WHO grade III or IV MG; solitary tumor; ≥4 weeks after chemotherapy, bevacizumab or study drug; adequate organ function; and KPS &gt;70%. Two patients per dose level (DL) were to be enrolled in the dose escalation portion (dose range: 40ng/mL to 23,354ng/mL), followed by dose expansion at the selected phase 2 dose (DL13). RESULTS As of 6/07/2019, 51 patients have been treated; 10 patients on the phase 2 dose. Observed dose limiting toxicities include: grade 4 seizure (n=1) on DL3, grade 3 confusion and pyramidal tract syndrome (n=1) on DL13, and grade 4 cerebral edema (n=1) and grade 3 dysphasia (n=1) on DL17. Grade 3 or higher adverse events possibly related to D2C7-IT include: seizure (grade 4, n=2, grade 3, n=3), cerebral edema (grade 4, n=1), hydrocephalus (grade 3, n=5), headache (grade 3, n=4), hemiparesis (grade 3, n=4), dysphasia (grade 3, n=4), lymphopenia (grade 3, n=3), thromboembolic event (grade 3, n=3); and one each of grade 3 elevated ALT, urinary tract infection, fall, wound complication, generalized muscle weakness, confusion, encephalopathy, and somnolence. Fourteen patients are alive. Three patients have partial radiographic response and remain alive without additional therapy more than 46, 27 and 21 months after D2C7-IT infusion. CONCLUSION Dose level 13 was selected as the optimal phase 2 dose and patient accrual is ongoing on the dose expansion arm. Encouraging efficacy results have been observed. A trial of D2C7-IT with checkpoint inhibitor is planned to start in the near future.

Clinical features of multiple sclerosis in third central hospital, Mongolia

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by inflammatory demyelinating and secondary axonal degeneration. The disease usually begins between the ages of 20 and 50 and is twice as common in women as in men. The aim of the study is to determine the clinical characteristics and features of the MS. The study was carried out in the patient history of the Neurology Department, The Third Central Hospital, Mongolia January 2014 to January 2017 by using a retrospective cohort study. In total, 37 patients were diagnosed with MS. Out of total 86.5% (32) patients are females and 13.5% (5) are male. In ages, the youngest of the patients is 23 years old, the oldest is 69 years old and the average age is 47.4 ± 13.3. The first symptom of the disease is 27% of all patients with one side optic neuritis, 18.9% of the pyramidal syndrome, 16.2% changes in the sensory symptoms, 13.5% ocular-motor dysfunction, 10.8% with bladder dysfunction, bulbar and ataxic syndromes were fewer. By the clinical type, cerebra-spinal form is 56.8%, the spinal form is 27%, the cerebral form is 13.5%, and the optical form is 2.7%. In the future, we will study the clinical characteristics of MS and establish the clinical database of the disease among the Mongolian population.