Syndrome Neuropathy Research Articles

Eye Signs in Stroke.

A large part of the central nervous system is involved in the normal functioning of the vision, and hence vision can be affected in a stroke patient. Transient visual symptoms can likewise be a harbinger of stroke and prompt rapid evaluation for the prevention of recurrent stroke. A carotid artery disease can manifest as transient monocular visual loss (TMVL), central retinal artery occlusion (CRAO), anterior ischemic optic neuropathy or ocular ischemic syndrome (OIS). Stroke posterior to the optic chiasm can cause sectoranopias, quadrantanopias, or hemianopias, which can be either congruous or incongruous. Any stroke involving the dorsal stream (occipito-parietal lobe), or ventral stream (occipito-temporal lobe) can manifest with visuospatial perception deficits. Similarly, different ocular motility abnormalities can result from a stroke affecting the cerebrum, cerebellum, or brainstem. Among these deficits, vision and perception disorders are more difficult to overcome. Clinical, experimental, and neuroimaging studies have helped us to understand the anatomical basis, physiological dysfunction, and the underlying mechanisms of these neuro-ophthalmic signs.

Identification of novel differentially expressed genes in type 1 diabetes mellitus complications using transcriptomic profiling of UAE patients: a multicenter study

Type 1 diabetes mellitus (T1DM) is a chronic metabolic disorder that mainly affects children and young adults. It is associated with debilitating and long-life complications. Therefore, understanding the factors that lead to the onset and development of these complications is crucial. To our knowledge this is the first study that attempts to identify the common differentially expressed genes (DEGs) in T1DM complications using whole transcriptomic profiling in United Arab Emirates (UAE) patients. The present multicenter study was conducted in different hospitals in UAE including University Hospital Sharjah, Dubai Hospital and Rashid Hospital. A total of fifty-eight Emirati participants aged above 18 years and with a BMI < 25 kg/m2 were recruited and forty-five of these participants had a confirmed diagnosis of T1DM. Five groups of complications associated with the latter were identified including hyperlipidemia, neuropathy, ketoacidosis, hypothyroidism and polycystic ovary syndrome (PCOS). A comprehensive whole transcriptomic analysis using NGS was conducted. The outcomes of the study revealed the common DEGs between T1DM without complications and T1DM with different complications. The results revealed seven common candidate DEGs, SPINK9, TRDN, PVRL4, MYO3A, PDLIM1, KIAA1614 and GRP were upregulated in T1DM complications with significant increase in expression of SPINK9 (Fold change: 5.28, 3.79, 5.20, 3.79, 5.20) and MYO3A (Fold change: 4.14, 6.11, 2.60, 4.33, 4.49) in hyperlipidemia, neuropathy, ketoacidosis, hypothyroidism and PCOS, respectively. In addition, functional pathways of ion transport, mineral absorption and cytosolic calcium concentration were involved in regulation of candidate upregulated genes related to neuropathy, ketoacidosis and PCOS, respectively. The findings of this study represent a novel reference warranting further studies to shed light on the causative genetic factors that are involved in the onset and development of T1DM complications.

Procedural Technique for Wide Awake Local Anesthesia No Tourniquet Injection for Endoscopic Carpal Tunnel Release

Carpal tunnel syndrome is the most common upper extremity peripheral neuropathy syndrome. Treatment ranges from nonsurgical methods, including night-orthosis fabrication and corticosteroid injections to surgical management via a carpal tunnel release (CTR). Carpal tunnel release alleviates nerve compression by releasing the transverse carpal ligament, and performed as either an open CTR (OCTR) or endoscopic CTR (ECTR) procedure. However, there is no consensus on the superiority of the 2 approaches. Practitioners may be limited to 1 technique because of surgeons' comfort, access to an operating room versus a procedure room, and cost. The purpose of this article was to describe the surgical technique for wide awake, local anesthesia, no tourniquet ECTR performed in an office-based setting, which would decrease operating room demand and cost.

Cognitive impairment is not uncommon in patients with biallelic RFC1 AAGGG repeat expansion, but the expansion is rare in patients with cognitive disease

IntroductionThe biallelic repeat expansion (AAGGG)exp in RFC1 causes cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). Recently, cognitive impairment has been reported in patients with CANVAS and a broader neurodegenerative process associated with RFC1 has been suggested. Furthermore, rare cases of multiple system atrophy, Parkinson's disease, amyotrophic lateral sclerosis or CANVAS with features of dementia with Lewy bodies have been found. ObjectiveWe hypothesized that the biallelic (AAGGG)exp is associated with neurodegeneration manifested as cognitive symptoms and that atypical RFC1 disease may be found among patients with cognitive disorder. MethodsClinical data on nine patients with biallelic (AAGGG)exp were reviewed and 564 patients with Alzheimer's disease or frontotemporal dementia (FTD) were investigated for biallelic RFC1 (AAGGG)exp. ResultsFive patients with biallelic (AAGGG)exp were found with a cognitive impairment and in four of them the phenotype resembled FTD. However, biallelic (AAGGG)exp was not detected among patients with Alzheimer's disease or FTD. ConclusionCognitive impairment is a feature in patients with the biallelic (AAGGG)exp, but the pathogenic expansion seems to be rare in patients with dementia. Studies on patients with diverse phenotypes would be useful to further explore the involvement of RFC1 in neuronal degeneration and to identify atypical phenotypes, which should be taken into account in clinical practice.

P11.71.B Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) in a patient with blastic plasmacytoid dendritic cell neoplasm: a rare neurologic manifestation in a rare disease

Abstract Background Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive myeloid hematological malignancy. Skin lesions, bone marrow, lymph nodes or visceral organs can be involved. 30% of patients will have infiltration to the nervous system,occult asymptomatic infiltration is frequent. Immunophenotype express CD4, CD56, and CD123, and flow cytometry is essential. Material and Methods 70-yo Hispanic male with a 1-month history of multiple violaceous cutaneous nodules and adenopathies.Neurological complaints included diplopia, hypoesthesia in the left face, dysphagia, gait difficulties, and generalized weakness with distal hypoesthesia. Examination revealed multiple cranial neuropathy (bilateral VI and VII nerve palsies, left V3 and VIII palsies and IX, X involvement), global areflexia, length-dependent weakness, ataxic gait and cerebellar syndrome. An inguinal ganglionar biopsy retrieved cells positive for CD4, TCL1, CD68 and CD123, whereas CD3, CD20, CD7, CD8, CD30 and myeloperoxidase were negative. PET/CT showed multiple supra and infradiaphragmatic adenopathies, bilateral pleural, pericardial and abdominal implants. Bone marrow biopsy was negative. Brain MRI showed contrast enhancement in the cerebellar folia and in the roots of the cranial nerves clinically involved. Multiple CSFs demonstrated high protein count (281- 310mg/dl), normal glucose and cell count; CSF flow cytometry and cytology reported no blastic infiltration (negative CD4, CD56 and CD123), CSF onconeuronal antibodies were negative. Nerve conduction studies fulfilled definite electrodiagnostic EFNS criteria for CIDP. Sural nerve biopsy reported inflammatory demyelination without infiltration. Systemic chemotherapy (Cyclophosphamide/Vincristine) with intrathecal cytarbine/methotrexate was administered. Results Favorable initial, but brief response was noticed for the cranial nerves and gait. He had neurological relapse with gait impossibility. Neuraxis MRI showed no contrast enhancement in the brain but new contrast enhancement of lumbosacral roots. Nerve conduction studies reported severe worsening criteria of CIDP. The PET/CT demonstrated complete response. Five days of methylprednisolone (1gr IV) followed by oral prednisone were prescribed (50 mg qd). However, two weeks later he suffered clinical neurological worsening with respiratory failure. IVIg was started (.4g/kg/day for 5 days) with no improvement; palliative care decision was consented. Conclusion We report the case of an adult male with multiple cranial nerve palsy, cerebellar syndrome and refractory rapidly progressive asymmetric polyneuropathy with BPDCN. CIDP in the absence of multiple attempts to demonstrate nervous system infiltration led us to consider this as a paraneoplastic phenomenon refractory to treatment. To our knowledge no CIDP has been reported in this rare disease

RFC1-Related Disease: Molecular and Clinical Insights.

In 2019, a biallelic pentanucleotide repeat expansion in the gene encoding replication factor C subunit 1 (RFC1) was reported as a cause of cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). In addition, biallelic expansions were shown to account for up to 22% of cases with late-onset ataxia. Since this discovery, the phenotypic spectrum reported to be associated with RFC1 expansions has extended beyond the initial conditions to include pure cerebellar ataxia, isolated somatosensory impairment, combinations of the 2, and parkinsonism, leading to a potentially broad differential diagnosis. Genetic studies suggest RFC1 expansions may be the most common genetic cause of ataxia and are likely underdiagnosed. This review summarizes the current molecular and clinical knowledge of RFC1-related disease, with a focus on the evaluation of recent phenotype associations and highlighting the current challenges in clinical pathways to diagnosis and molecular testing.

Pattern of adverse drug reactions to anticancer drugs at an apex hospital in south India: A retrospective study

Cancer chemotherapy is rampant as cancer is the 2nd most common cause of global mortality. It is challenged by a horde of adverse drug reactions (ADRs) and adverse events. A proper study of these ADRs is very crucial to limit their occurrences and thereby ameliorate the sufferings of the patients. Our study was to assess the frequency, nature and profile of the ADRs with anticancer drugs. A retrospective analysis of the ADR data collected over a period of 5 years was considered. Demography, drug related changes and clinical details of the patients were recorded and analysed. A total of 1145 ADR events were reported during the study period of January 01, 2017 to December 31st 2021 of which 232 cases (20.26 %) were due to anticancer drugs. The majority of the ADRs were accounted in females and in the elderly age group (&amp;#62;60 years). The commonly reported ADRs included breathing difficulty, chest discomfort, itching all over the body, numbness, neuropathy, mucositis and hand foot syndrome. The most common drugs that caused ADRs were Platinum coordination complex drugs, Taxanes, Rituximab and pyrimidine antagonists like Capecitabine and Gemcitabine. Causality assessment done using WHO-Uppsala Monitoring Centre causality assessment scale which showed 69.4% cases as “probable”, 29.3% cases as “possible” and 1.3% as “certain”. Severity assessed using the modified Hartwig and Siegel scale showed most of the cases as of moderate severity. Most of the ADR events in our study was manageable although a few required the withdrawal of the causative drug. Rigorous monitoring and adequate reporting are very crucial for the prompt identification, assessment and timely management of ADRs in the patients receiving chemotherapy so as to improve the quality of life in these patients.

Genetic and clinical features of cerebellar ataxia with RFC1 biallelic repeat expansions in Japan

The recessive intronic pentanucleotide repeat AAGGG expansion of replication factor complex subunit 1 (RFC1) is associated with cerebellar ataxia, sensory neuropathy, and vestibular areflexia syndrome. And the clinical spectrum has been continuously expanding. We conducted this study to demonstrate the clinical and genetic features of a large-scale case series of Japanese patients with cerebellar ataxia with RFC1 repeat expansions. We examined 1,289 Japanese patients with cerebellar ataxia and analyzed RFC1 repeat expansions in 840 patients, excluding those with genetic diagnoses or an autosomal dominant inheritance pattern. For individuals where no product was obtained by flanking polymerase chain reaction (PCR), repeat-primed PCR was performed using primers specific for the following four repeat motifs: AAAAG, AAAGG, AAGGG, and ACAGG. RFC1 analysis revealed multitype biallelic pathogenic repeat expansions in 15 patients, including (AAGGG)exp/(AAGGG)exp in seven patients, (ACAGG)exp/(ACAGG)exp in three patients, (AAGGG)exp/(ACAGG)exp in four patients, and (AAGGG)exp/(AAAGG)15(AAGGG)exp in one patient. Clinical analysis showed various combinations of cerebellar ataxia, vestibular dysfunction, neuropathy, cognitive decline, autonomic dysfunction, chronic cough, pyramidal tract disorder, parkinsonism, involuntary movement, and muscle fasciculation. Pathological RFC1 repeat expansions account for 1.8% (15/840) of undiagnosed patients with cerebellar ataxia and sporadic/recessive/unclassified inheritance. Screening of RFC1 repeat expansions should be considered in patients with cerebellar ataxia, irrespective of their subtype and onset age.

RFC1 nonsense and frameshift variants cause CANVAS: clues for an unsolved pathophysiology.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is an inherited late-onset neurological disease caused by bi-allelic AAGGG pentanucleotide expansions within intron 2 of RFC1. Despite extensive studies, the pathophysiological mechanism of these intronic expansions remains elusive. We screened by clinical exome sequencing two unrelated patients presenting with late-onset ataxia. A repeat-primer polymerase chain reaction was used for RFC1 AAGGG intronic expansion identification. RFC1 mRNA expression was assessed by quantitative reverse transcription-polymerase chain reaction. We identified the first two CANVAS affected patients who are compound heterozygous for RFC1 truncating variants (p.Arg388* and c.575delA, respectively) and a pathological AAGGG expansion. RFC1 expression studies in whole blood showed a significant reduction of RFC1 mRNA for both patients compared to three patients with bi-allelic RFC1 expansions. In conclusion, this observation provides clues that suggest bi-allelic RFC1 conditional loss-of-function as the cause of the disease.

Prevalence and factors associated with latent autoimmune diabetes in adults (LADA): a cross-sectional study

BackgroundThe Latent Autoimmune Diabetes in Adults (LADA) is a slowly progressive Type 1 diabetes subgroup with onset during middle age. Studies report that about 10% of adults initially diagnosed with clinical Type 2 diabetes (T2D) have LADA. Inappropriate diagnosis and mismanagement of the LADA can increase the risk of diabetic complications, which affect the quality of life and is the cause of increased mortality. In low-income countries setting, data regarding the magnitude of LADA is limited. We carried out this study to estimate the burden of misdiagnosed LADA among T2D patients in selected health facilities in Dar es Salaam and to bring awareness to the use of Glutamic Acid Decarboxylase (GAD) autoantibody in screening for LADA.MethodologyWe enrolled 186 phenotypically T2D patients in this cross-sectional study, through a standardized data collection tool we obtained participants’ demographic and clinical information. For testing GAD levels, we used a double-antibody Enzyme-Linked Immunosorbent Assay (ELISA). The Fisher’s Exact and student t-tests were used to test the significance of the statistical associations of the glycaemic control and diabetes complications between T2D and LADA.ResultsOut of 186 patients, 156 gave conclusive GAD Ab ELISA reading with LADA accounting for 5.1% (95% CI: 2.5 - 10.0). The mean age of subjects was 54.3 years (Range: 33-85 years). The parameters such as mean age, family history of diabetes mellitus status, Fasting Blood Glucose, clinical characteristics, and complications did not show significant statistical differences between patients with LADA and Type 2 diabetes. However, all LADA- Human Immunodeficiency Virus (HIV) comorbid patients had retinopathy, which was statistically insignificant in 20 (87%) T2D-HIV comorbid patients (p = 0.669). Neither neuropathy, nephropathy, nor Diabetic Mellitus (D.M.) foot syndrome was observed among LADA-HIV comorbid patients. Nevertheless, 22 (95.7%), 3 (13%), and 2 (8.7%) of T2D-HIV comorbidity had neuropathy, nephropathy, or D.M. foot syndrome, respectively.ConclusionsThe study established a LADA prevalence of 5.1% among T2D patients and has shown the role of GAD autoantibody in the screening for LADA. The study calls for a well- designed larger longitudinal study to generate strong evidence on the association of risk factors and complications associated with the LADA. This will develop robust evidence on the association of risk factors and complications associated with the LADA and T2D.

Reduced penetrance of an eastern French mutation in ATL1 autosomal-dominant inheritance (SPG3A): extended phenotypic spectrum coupled with brain 18F-FDG PET.

ATL1-related spastic paraplegia SPG3A is a pure form of hereditary spastic paraplegia. Rare complex phenotypes have been described, but few data concerning cognitive evaluation or molecular imaging of these patients are available. We relate a retrospective collection of patients with SPG3A from the Neurology Department of Nancy University Hospital, France. For each patient were carried out a 18F-FDG PET (positron emission tomography), a electromyography (EMG), a sudoscan®, a cerebral and spinal cord MRI (magnetic resonance imaging) with measurement of cervical and thoracic surfaces, a neuropsychological assessment. The present report outlines standardised clinical and paraclinical data of five patients from two east-France families carrying the same missense pathogenic variation, NM_015915.4(ATL1): c.1483C > T p.(Arg495Trp) in ATL1. Mean age at onset was 14 ± 15.01years. Semi-quantitatively and in comparison to healthy age-matched subjects, PET scans showed a significant cerebellar and upper or mild temporal hypometabolism in all four adult patients and hypometabolism of the prefrontal cortex or precuneus in three of them. Sudoscan® showed signs of small fibre neuropathy in three patients. Cervical and thoracic patients' spinal cords were significantly thinner than matched-control, respectively 71 ± 6.59mm2 (p = 0.01) and 35.64 ± 4.35mm2 (p = 0.015). Two patients presented with a dysexecutive syndrome. While adding new clinical and paraclinical signs associated with ATL1 pathogenic variations, we insist here on the variable penetrance and expressivity. We report small fibre neuropathy, cerebellar hypometabolism and dysexecutive syndromes associated with SPG3A. These cognitive impairments and PET findings may be related to a cortico-cerebellar bundle axonopathy described in the cerebellar cognitive affective syndrome (CCAS).

Prevalence of Delayed Neuropathy and Intermediate Syndrome in Acute Organophosphorus Poisoning: A Cross-sectional Toxicological/Clinical Study

Background: Organophosphates are among the most common causes of poisoning worldwide—responsible for 3 million poisoning and 200000 deaths every year. Nearly 15% of people who are poisoned die. This cross-sectional toxicological/clinical study aimed to investigate the prevalence and influential factors in the incidence of delayed peripheral neuropathy and intermediate syndrome in acute poisoning with organophosphorus toxins. The study was conducted in Loghman Hakim Hospital, Tehran City, Iran, from 2017 to 2020. Methods: The study data were obtained from the patients’ records during follow-up. Data included demographic information (age, sex, etc.), vital signs, muscarinic, nicotinic, and neurological symptoms at admission, atropine therapy status, and pralidoxime intake status. Post-discharge complications were obtained, and patients’ Electromyography (EMG) and Nerve Conduction Velocity (NCV) results were recorded and evaluated during hospitalization and follow-up. Statistical analysis was performed using SPSS software, version 22. Results: Of 63 studied patients, 61.9% were female. The Mean±SD age of the patients was 31.90±13.128 years. Male patients were significantly (P&lt;0.010) older than female ones. The most common muscarinic symptoms were nausea and vomiting (73.2%), diarrhea (34.92%), and abdominal pain (33.33%). Regarding the nicotinic symptoms, sweating (30.16%) and fasciculation (19.05%) were the commonest. Neurological complications were less common; seizures were observed in 3 cases (4.76%) and coma in 2 cases (3.17%). Most patients (79.4%) received pralidoxime with atropine. The Mean±SD days of treatment with atropine and pralidoxime were 5.51±3.52 and 4.06±4.62 days, respectively. Only one death was recorded. The results of the initial EMG-NCV test on the second day of hospitalization showed abnormalities in 4 patients (6.3%), indicating the presence of the intermediate syndrome. Conclusion: The results of the EMG-NCV tests at our patients’ follow-up (30 days) showed no abnormalities. Hence no cases of delayed neuropathy were seen. During hospitalization, one patient had flaccid paralysis and showed significant impairment on the EMG-NCV test (P&lt;0.01).

Syndrome of venous compression neuropathy in patients with pelvic varicose veins

The study objective is to investigate the pathogenesis of the development of pelvic symptoms in patients with pelvic varicose veins.Materials and methods. From 2015 to 2022, 145 men with pelvic varicose veins were examined. The examination included questioning of patients using questionnaires (scales) and instrumental methods: 1) ultrasound examination of the scrotum with color Doppler mapping; 2) transrectal ultrasound examination of the prostate and veins of the periprostatic plexus; 3) magnetic resonance imaging of the inferior vena cava and pelvic vessels or computer (multispiral) tomography of the abdominal organs with contrast; 4) phlebography of the renocaval and ileocaval segments.Results. The variant anatomy of fibrous and fibro-osseous canals (tunnels) can explain the fact that with equally pronounced expansion of the pelvic veins, some patients have pelvic symptoms due to nerve compression, while the other part does not. This concept is supported by the fact that in those patients who had complaints of pain, dysuria and erectile dysfunction, after surgical treatment of pelvic varicose veins, in most cases they disappeared or decreased.Conclusion. Pain syndrome (56.6 % of cases), erectile dysfunction (51 % of cases) and dysuria (17.9 % of cases) were noted as clinical manifestations in patients with pelvic varicose veins. Analysis of data after examination and treatment of patients with pelvic varicose veins allowed us to identify “venous compression neuropathy syndrome” as a probable cause of the development of pelvic symptoms in patients with pelvic varicose veins. Depending on the level of localization of nerve compression by varicose veins, we proposed to distinguish three forms of this syndrome: 1) thoracic, 2) lumbar, and 3) sacral form.

Head impulse testing in bilateral vestibulopathy in patients with genetically defined CANVAS.

BackgroundTo investigate the association between disease duration and the severity of bilateral vestibulopathy in individuals with complete or incomplete CANVAS (Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome) and biallelic RFC1 repeat expansions.MethodsRetrospective analysis of clinical data and the vestibulo‐ocular reflex quantified by the video head impulse test in 20 patients with confirmed biallelic RFC1 repeat expansions.ResultsVestibulo‐ocular reflex gain at first admittance 6.9 ± 5.0 years after disease onset was 0.16 [0.15–0.31] (median [interquartile range]). Cross‐sectional analysis revealed that gain reduction was associated with disease duration. Follow‐up measurements were available for ten individuals: eight of them exhibited a progressive decrease of the vestibulo‐ocular reflex gain over time. At the first visit, six of all patients (30%) did not show clinical signs of cerebellar ataxia.ConclusionsOur data suggest a pathological horizontal head impulse test, which can easily be obtained in many outpatient clinics, as a sign of bilateral vestibulopathy in genetically confirmed CANVAS that can precede clinically accessible cerebellar ataxia at least in a subset of patients. The presumably continuous decline over time possibly reflects the neurodegenerative character of the disease. Thus, genetic testing for RFC1 mutations in (isolated) bilateral vestibulopathy might allow disease detection before the onset of cerebellar signs. Further studies including a wider spectrum of vestibular function tests are warranted in a prospective design.

A novel TRMT5 mutation causes a complex inherited neuropathy syndrome: The role of nerve pathology in defining a demyelinating neuropathy.

We aim to present data obtained from three patients belonging to three unrelated families with an infantile onset demyelinating neuropathy associated to somatic and neurodevelopmental delay and to describe the underlying genetic changes. We performed whole-exome sequencing on genomic DNA from the patients and their parents and reviewed the clinical, muscle and nerve data, the serial neurophysiological studies, brain and muscle MRIs, as well as the respiratory chain complex activity in the muscle of the three index patients. Computer modelling was used to characterise the new missense variant detected. All three patients had a short stature, delayed motor milestone acquisition, intellectual disability and cerebellar abnormalities associated with a severe demyelinating neuropathy, with distinct morphological features. Despite the proliferation of giant mitochondria, the mitochondrial respiratory chain complex activity in skeletal muscle was normal, except in one patient in whom there was a mild decrease in complex I enzyme activity. All three patients carried the same two compound heterozygous variants of the TRMT5 (tRNA Methyltransferase 5) gene, one known pathogenic frameshift mutation [c.312_315del (p.Ile105Serfs*4)] and a second rare missense change [c.665 T > C (p.Ile222Thr)]. TRMT5 is a nuclear-encoded protein involved in the post-transcriptional maturation of mitochondrial tRNA. Computer modelling of the human TRMT5 protein structure suggests that the rare p.Ile222Thr mutation could affect the stability of tRNA binding. Our study expands the phenotype of mitochondrial disorders caused by TRTM5 mutations and defines a new form of recessive demyelinating peripheral neuropathy.

Historical Perspective and Medical Maladies of Alexander the Great.

Alexander the Great (356 BC - 323 BC) was only 20 years old when he was named the next King of Macedonia after his father was assassinated. The following 11 years witnessed the evolution of an outstanding leader who expanded his empire from Egypt to the Indian frontier. Despite successfully conquering much of the world, he was afflicted with a febrile illness at the age of 32, which he battled for a mere 11 days before perishing. It has been almost 2,400 years since his death, but the exact cause remains a mystery. Did he die of natural causes or at the hands of conspirators? Numerous papers have been written about the illnesses suffered by Alexander, with the current evidence revealing a healthy 32-year-old man who developed fever and acute abdominal pain with rapid deterioration of his general condition leading to death within a short duration. We analyze various theories and discuss possible etiologies that may have contributed to his tragic death. Information was gathered from primary and secondary sources found through searching multiple online academic databases and the University of Southern California (USC), University of California Los Angeles (UCLA), and Harvard libraries. Unreliable sources and the unavailability of Alexander’s body for autopsy make reaching a definitive diagnosis an impossible task; however, based on existing information, we presume that he most probably died of a neurological cause due to acute necrotizing pancreatitis and encephalopathy secondary to peritonitis. Other potential causes include fulminant hepatic failure, acute demyelinating neuropathy or Guillain Barre Syndrome, and arsenic poisoning.

Patient reported outcomes following revision neurectomy through a dorsal approach for recurrent interdigital neuroma

Interdigital neuroma is one of the commonest causes of metatarsalgia. The reported success rate after excision of a primary neuroma is 74%. Recurrent symptoms after neurectomy can be due to a recurrent interdigital neuroma. Recurrent interdigital neuromas can be diagnosed using sound clinical examination and ultrasonography. Surgical excision is the best treatment modality with varying success reported in the literature. We report on the clinical outcome following surgical excision of recurrent interdigital neuromas through a dorsal approach. All patients who had undergone excision of a recurrent interdigital neuroma by a single surgeon between 01/2010 and 12/2019 were identified. Inclusion criteria included patients having a preoperative ultrasound and postoperative histology report. The exclusion criteria were preexisting neuropathy or tarsal tunnel syndrome. Demographic data was collected, and a self-reported foot and ankle score questionnaire (SEFAS) was completed by the patient at their most recent follow-up. Twenty-three patients (25 feet) were included in the study. Mean time of follow-up was 75 (range 14–189) months. The mean age was 49 (range 15–71) years. Eleven (44%) recurrent neuromas were excised from the second webspace and 14 (56%) were excised from the third webspace. All excised masses were confirmed as recurrent neuromas histologically. Regarding the SEFAS score, 17 (73.93%) patients scored as excellent, one (4.34%) as good, three (13.04%) as fair, and two (8.69%) as poor. This long term follow-up study on outcomes after surgery for recurrent interdigital neuroma suggests that excision through a dorsal approach is an effective treatment option with a high patient satisfaction.

CEDNIK Syndrome, a Rare Neuro-Cutaneous Disorder in an Iranian Patient: Case Report and Review of Specific Neuro-Ichthyotic Syndromes

Cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK) syndrome is an autosomal recessive neuro-cutaneous disorder characterized by a collection of clinical manifestations, including microcephaly, cerebral dysgenesis, palmoplantar keratoderma, facial dysmorphism, and ichthyosis. The etiology of this condition has been proved to be a homozygous mutation in the SNAP29 gene, which has an essential role in dermatological and neurological manifestations of this syndrome. In this report, we present the first documented Iranian patient with CEDNIK syndrome. So far, only 14 cases of this condition have been reported globally.

RFC1 repeat expansions: A recurrent cause of sensory and autonomic neuropathy with cough and ataxia.

Ataxia and cough are rare features in hereditary sensory and autonomic neuropathies (HSAN), a group of diseases of mostly unknown genetic cause. Biallelic repeat expansions in RFC1 are associated with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study aimed to investigate the prevalence of RFC1 repeat expansions in a cohort of HSAN patients. After unremarkable whole-exome sequencing (WES) analysis, we performed repeat-primed PCR to detect intronic RFC1 expansions in 12 HSAN families, who all presented with chronic cough. In these patients, 75% carried biallelic expansions of the pathogenic AAGGG motif. Compared with RFC1-/- cases, RFC1+/+ cases presented more consistently with positive sensory and autonomic symptoms. Afferent ataxia was more severe in the RFC1+/+ cohort and cerebellar ataxia was a common feature (21%). We demonstrate that RFC1 is a frequent cause of (WES-negative) HSAN with chronic cough and ataxia. The diagnostic yield of RFC1 repeat-primed PCR was surprisingly high, given that HSAN is genetically poorly understood. This combination of HSAN, ataxia, and chronic cough symptoms represents a new nosological entity within the neuropathy-ataxia spectrum.

Anatomical Variations of the Suprascapular Notch and Its Importance in Nerve Entrapment

Background and Aim: Entrapped neuropathy syndrome could be effectively managed with detailed anatomical knowledge of suprascapular notch. Suprascapular nerve injuries are now widely acknowledged as a cause of shoulder pain and dysfunction. The present study aimed to determine the anatomical variation of the suprascapular notch and its importance in nerve entrapment. Methodology: A total of 128 human scapulae of either gender were taken from the department of Anatomy, Saidu Group of Teaching Hospitals, Swat and Women Medical and Dental College Hospital Abbottabad during the period from January to June, 2021. Four parameters of Suprascapular notch (SSN) i) Superior transverse depth (STD), ii) Maximum depth (MD), iii) middle transverse diameter (MTD), and total circumferential diameter (TCD) were defined based on incisura inferior border shape and vertical diameters. Suprascapular notch presence or absence was grossly examined for all the scapulae. Vernier caliper was used for the measurement of the four suprascapular notch parameters. SPSS version 23 was used for data analysis. Results: Out of 128, 61 (47.7%) were right-sided and 67 (52.3%) were left-sided human scapulae. The prevalence of U-shaped, V-shaped, and J-shaped notch were 62 (48.4%), 27 (21.1%), and 13 (10.2%) respectively. The incidence of the large double foramen, complete, and incomplete suprascapular notch were 2 (1.6%), 7 (5.5%), and 8 (6.3%) respectively. W-notched was present in 3 (2.3%) scapulae whereas 6 (4.7%) scapulae had no notch. The vertical and transverse diameters for right and left-sided type-II scapulae were 4.9±2.1 mm and 8.9±3.1 mm and 4.8±1.7 mm and 9.1±2.3 mm respectively. Conclusion: The prevalence of U-shaped and V-shaped notch was 48.4% and 21.1% respectively. Suprascapular notch morphology could be determined with anatomical knowledge and play a critical role for neurosurgeons, clinicians, orthopedic surgeons, and radiologists for proper diagnosis and management of shoulder region surgical procedure and protocol. Keywords: Suprascapular notch, Anatomical knowledge, Nerve entrapment