Demyelinating Sensorimotor Polyneuropathy Research Articles

Late Onset of Severe Demyelinating Peripheral Neuropathy in a 62-Year-Old African American Woman.

Hereditary neuropathies are typically associated with an early onset of symptoms, but same types of neuropathies may also manifest late, after the age 50 years. A 62-year-old African American woman presented with a 6-year history of gait unsteadiness and has been using a walker since the age 57 years after an unwitnessed fall. Gradual worsening of walking difficulties was later followed by decreased dexterity. The family history was negative for neuromuscular disorders, including neuropathy. On examination, the patient had both distal and proximal weakness with distal sensory loss to all modalities and hyporeflexia. Charcot Marie Tooth Examination Score was 12. Previous electrodiagnostic testing at the age 60 years showed severe sensorimotor demyelinating polyneuropathy with bilateral severe carpal tunnel syndrome. Genetic testing showed a homozygous pathogenic mutation in SH3TC2 gene (c.2860C>T; p.Arg954*), associated with CMT4C. CMT4C is the most common recessive demyelinating sensorimotor polyneuropathy and overall comprises 0.4%-1.7% of all patients with Charcot-Marie-Tooth disease. It is more common in French Canadians and Spanish Roma and in recent natural history study; only 1 of 56 patients was African American. This report demonstrates sporadic occurrence of CMT4C in other ethnic groups as well.

Chronic acquired polyneuropathy as presentation of skull based solitary bone plasmacytoma

Plasmacytomas can be solitary or multiple (osteosclerotic myeloma). Neuropathy resembling chronic inflammatory demyelinating polyradiculoneuropathy or POEMS syndrome has rarely been reported in literature in association of cranial vault plasmacytoma. A female patient with severe demyelinating sensori-motor polyneuropathy with conduction block, was found to have solitary skeletal lesion in the left frontal bone which confirmed to be a plasma cell neoplasm on biopsy. She had significant improvement in neurological signs and symptoms following local radiation and chemotherapy over next 3 months. Solitary bone plasmacytoma (SBP) is rare, accounting for 2-5% of all plasma cell neoplasms. The axial skeleton, especially vertebral body, is the most common site and cranial vault is one of the least commonly reported. Radiation therapy (RT) is the treatment of choice for SBP. There is no evidence that plasma exchange, IVIg or other immunosuppressive agents are effective when used alone in treatment of SBP-associated neuropathy.

Distinctive gastrointestinal motor dysfunction in patients with MNGIE.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare mitochondrial disease caused by mutations in TYMP, encoding thymidine phosphorylase. Clinically it is characterized by severe gastrointestinal dysmotility associated with cachexia and a demyelinating sensorimotor polyneuropathy. Even though digestive manifestations are progressive and invariably lead to death, the features of gastrointestinal motor dysfunction have not been systematically evaluated. The objective of this study was to describe gastrointestinal motor dysfunction in MNGIE using state-of-the art techniques and to evaluate the relationship between motor abnormalities and symptoms. Prospective study evaluating gastrointestinal motor function and digestive symptoms in all patients with MNGIE attended at a national referral center in Spain between January 2018 and July 2022. In this period, five patients diagnosed of MNGIE (age range 16-46 years, four men) were evaluated. Esophageal motility by high-resolution manometry was abnormal in four patients (two hypoperistalsis, two aperistalsis). Gastric emptying by scintigraphy was mildly delayed in four and indicative of gastroparesis in one. In all patients, small bowel high-resolution manometry exhibited a common, distinctive dysmotility pattern, characterized by repetitive bursts of spasmodic contractions, without traces of normal fasting and postprandial motility patterns. Interestingly, objective motor dysfunctions were detected in the absence of severe digestive symptoms. MNGIE patients exhibit a characteristic motor dysfunction, particularly of the small bowel, even in patients with mild digestive symptoms and in the absence of morphological signs of intestinal failure. Since symptoms are not predictive of objective findings, early investigation is indicated.

Expanding the Molecular Spectrum of HK1-Related Charcot-Marie-Tooth Disease, Type 4G; the First Report in Iran.

Charcot-Marie-Tooth disease type 4G (CMT4G) was first reported in Balkan Gypsies as a myelinopathy starting with progressive distal lower limb weakness, followed by upper limb involvement and prominent distal sensory impairment later in the patient's life. So far, CMT4G has been only reported in European Roma communities with two founder homozygous variants; g.9712G>C and g.11027G>A, located in the 5'-UTR of the HK1 gene. Here, we present the first Iranian CMT4G patient manifesting progressive distal lower limb weakness from 11 years of age and diagnosed with chronic demyelinating sensorimotor polyneuropathy. Whole-exome sequencing for this patient revealed a homozygous c.19C>T (p. Arg7*) variant in the HK1 gene. This report expands the mutational spectrum of the HK1-related CMT disorder and provides supporting evidence for the observation of CMT4G outside the Roma population. Interestingly, the same Arg7* variant is recently observed in another unrelated Pakistani CMT patient, proposing a possible prevalence of this variant in the Middle Eastern populations.

Inflammatory Polyneuropathy Associated with Myelodysplastic Syndrome

Inflammatory polyneuropathy may be associated with various tumorous diseases, including hematological malignancy. A 50-year-old man visited neurologic department complaining of bilateral lower extremities weakness, tingling sensation and weight loss. Initially he was diagnosed as demyelinating sensorimotor polyneuropathy after performing the nerve conduction study, furthermore myelodysplastic syndrome was revealed by the hematologic tests and bone marrow examination. Conclusively, high-dose steroid therapy, intravenous immunoglobulin and chemotherapy improved neurological symptoms. This case suggests myelodysplastic syndrome could be uncommon cause of the inflammatory polyneuropathy.

Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin abnormalities (POEMS) Syndrome in a Filipino Nurse Returning to Work Following Bortezomib Treatment: A Case Report

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) also known as Crow-Fukase syndrome or Takatsuki syndrome is a rare and disabling paraneoplastic syndrome that frequently occurs in the fifth or sixth decade of life without a known standard first-line therapy. A 34-year-old Filipino male nurse, who presented with gradually progressive distal lower extremity weakness and sharp shooting pain in bilateral legs accompanied by mild joint effusion on the left knee, hypertrichosis, bilateral conjunctival injection, and gynecomastia underwent extensive workup and was diagnosed with POEMS syndrome. Complete blood count revealed erythrocytosis and thrombocytosis with elevated serum VEGF (vascular endothelial growth factor) and elevated monoclonal serum free lambda light chains. The electrophysiologic studies revealed chronic demyelinating sensorimotor polyneuropathy while bone marrow core biopsy and bone marrow aspirate smear immunohistochemical staining showed it to be positive for lambda and CD138. He had an initial unsuccessful treatment course with melphalan and prednisone. Hence, bortezomib and dexamethasone were given which gave significant improvement in symptoms from the overall neuropathy limitation score of 5 to 1.

106 Inflammatory peripheral neuropathy in haematological malignancies

BackgroundWe report the case of a 62-year-old female with demyelinating sensorimotor polyneuropathy in the context of lymphoplasmacytic lymphoma.Case Presentation62-year-old woman presenting with distal lower limb numbness bilaterally, with a 9-year progressive course. Over the next 3 years, foot drop developed with gradual lower and upper limb involvement.Investigations showed raised IgM paraprotein, 20 g/dL. Bone marrow biopsy identified 2-B cell clonal populations with positive MYD88 mutation in keeping with lymphoplasmacytic lymphoma (LPL). Neuro- physiological studies showed very severe length-dependent, sensorimotor neuropathy. She was VEGF/anti-MAG negative, but anti-GM2 positive. Widely-spaced myelin and moderate axonal loss were seen on sural nerve biopsy.She was diagnosed with a progressive demyelinating neuropathy in the context of LPL.Initial IVIG treatment failed.Second line treatment – cyclophosphamide/rituximab/dexamethasone, improved her lower limb weakness. Ibrutinib later stabilised her weakness in the lower but not upper limbs.Plexus nerve biopsy showed general inflammation, excluding direct clonal infiltration and amyloid deposi- tion. This reconfirmed the diagnosis: inflammatory neuropathy driven by a haematological malignancy. She received further treatment with rituximab-bendamustine.ConclusionUnderstanding the pathological mechanism of polyneuropathies in haematological malignan- cies is of paramount importance for choosing the most effective therapy, as illustrated by the above cas8e7.a.zirra@nhs.net

A case of brucellosis-induced Guillain\u2013Barre syndrome

BackgroundGuillain–Barre syndrome (GBS) is a rare neurological complication of brucellosis, and neurobrucellosis is the most common, but they have many similarities in clinical manifestations. Many clinicians are accustomed to merely explaining the manifestations of nervous system involvement with neurobrucellosis, but they ignore the possibility of GBS, and this leads to misdiagnosis, untimely treatment, and serious consequences.Case presentationA 55-year-old male patient was admitted to The First Affiliated Hospital of Harbin Medical University for intermittent fever, fatigue, and waist pain more than three months. Brucellosis was diagnosed from the blood test. Although anti-brucella treatment was given at the time of diagnosis, the disease continued to progress. At the time of the cerebrospinal fluid systematic physical examination and the neuroelectrophysiological test, acute motor sensory axonal neuropathy was diagnosed. The patient was given immediately administered immunoglobulin therapy. After three months of systemic treatment, the patient's muscle strength of the distal limbs gradually recovered. The numbness of the limbs eased slowly, and urination function and respiratory function returned to normal. He could sit by himself.ConclusionsThe possibility of GBS should be closely monitored for when a brucellosis patient shows typical clinical manifestations of progressive muscle weakness, protein-cell separation of the cerebral spinal fluid, and typical demyelinating sensorimotor polyneuropathy.

Stiff-person syndrome with sensorimotor polyneuropathy – case report

Stiff-person syndrome (SPS) is a rare disorder with an estimated prevalence in the general population of 1–2 cases/1,000,000. It is 2–3 times more common in females, with symptom onset at the age of 20–50 years in most cases. Although stiff-person syndrome is associated with antibodies against glutamic acid decarboxylase and amphiphysin, their presence is not necessary for the diagnosis. The treatment should be multidirectional and include immunomodulation, symptomatic treatment as well as monitoring and treatment of overlapping autoimmune, and surgery. We present a case report of a patient diagnosed with stiff-person syndrome overlapping with axonal and demyelinating sensorimotor polyneuropathy. The diagnostic workup indicated diabetes-related polyneuropathy. About 30% of patients diagnosed with stiff-person syndrome also have diabetes. Polyneuropathy alone is rarely reported to overlap with the disorder. In our opinion, polyneuropathy may have a beneficial effect on the clinical presentation of stiff-person syndrome.

GBE1‐related disorders: Adult polyglucosan body disease and its neuromuscular phenotypes

Adult polyglucosan body disease (APBD) represents a complex autosomal recessive inherited neurometabolic disorder due to homozygous or compound heterozygous pathogenic variants in GBE1 gene, resulting in deficiency of glycogen-branching enzyme and secondary storage of glycogen in the form of polyglucosan bodies, involving the skeletal muscle, diaphragm, peripheral nerve (including autonomic fibers), brain white matter, spinal cord, nerve roots, cerebellum, brainstem and to a lesser extent heart, lung, kidney, and liver cells. The diversity of new clinical presentations regarding neuromuscular involvement is astonishing and transformed APBD in a key differential diagnosis of completely different clinical conditions, including axonal and demyelinating sensorimotor polyneuropathy, progressive spastic paraparesis, motor neuronopathy presentations, autonomic disturbances, leukodystrophies or even pure myopathic involvement with limb-girdle pattern of weakness. This review article aims to summarize the main clinical, biochemical, genetic, and diagnostic aspects regarding APBD with special focus on neuromuscular presentations.

Neuromuscular manifestations of lead poisoning in opium and herbal users in Iran

Opium sale is prohibited in Iran, and sellers mix it with lead to increase the weight. Herein, we describe neuromuscular findings in nine patients who developed lead poisoning due to opium/drug consumption. The mean age of patients was 53±3.5 years and their mean blood lead level was 122.6±20.8μg/dL. Most of the patients had an acute/subacute course presenting as axonal or demyelinating sensorimotor polyneuropathy, motor neuron disease, and multiple mononeuropathies with favorable response to the chelation therapy. Lead poisoning should be considered in patients with a history of opium use and neuromuscular symptoms.

P84-F Subacute polyneuropathy partially responsive to immunomodulatory treatment coexisting with POLG mutation

Background During the last few years, the correlation between mitochondrial disorders and autoimmune diseases has been reported. Autoimmune polyneuropathies were concomitant with symptoms related to the polymerase γ (POLG) mutations. POLG is involved in mitochondrial DNA (mtDNA) replication and maintenance. Material and methods We present a case of a16-year-old girl with W748S mutation of POLG region with a 1,5-year history of slowly progressive walking difficulties. Results In the neurological examination the girl had ataxic gait with sensory disturbances in lower extremities with areflexia. Nerve conduction studies (NCS) demonstrated axonal–demyelinating sensorimotor polyneuropathy of the lower limbs. Additionally, magnetic resonance imaging (MRI) of the lumbar spine revealed gadolinium enhancement of the spinal roots and an examination of cerebrospinal fluid showed dissemination. The immunomodulatory treatment with intravenous methylprednisolone and intravenous immunoglobulin (IVIg) was started. Conclusions The IVIg and IVMP treatment led to marked improvement of her abnormal gait and improved resolution of abnormalities of touch, temperature sensation and improved proprioception. The W748S mutations were commonly reported and associated with variable phenotypes, most often Alpers syndrome, but also polyneuropathy. However, electrodiagnostic features and partial response to immunomodulatory therapy suggest the autoimmune etiology of the patients’ subacute symptoms. We hypothesize that oxidative stress caused by impaired mitochondria function may trigger an autoimmune response.

Severe neurologic complications of immune checkpoint inhibitors: a single-center review.

Immune checkpoint inhibitors (ICIs) are a promising class of anticancer drugs associated with immune-related adverse events (IRAEs). In registration studies of selected cancer populations, neurologic IRAEs were rare. Post-marketing experience describing their prevalence in clinical practice continues to be reported. A retrospective cohort of patients treated at our institution with ICIs from 2005 to 2017 was identified. Patients with new neurologic ICD codes documented during or after ICI treatment were enrolled. Comprehensive medical record review identified patients with neurologic IRAEs causally linked to ICIs. This study focused on CTCAE grade 2-4 IRAEs. 526 patients were screened; 55 candidate patients were identified; 5 cases met criteria for neurologic IRAEs, an incidence of 0.95% (n = 5/526). IRAEs identified were transverse myelopathy, demyelinating sensorimotor polyneuropathy, oculomotor nerve palsy, sensory neuropathy, and posterior reversible encephalopathy syndrome. ICIs were held in three patients, rechallenged in one, and dose-reduced in one. Corticosteroids were given in three patients, and response varied from complete symptom resolution to minimal response and ultimately death. Other treatments were based on IRAE presentation, including gabapentin, antihypertensives, and IV immunoglobulin. Patients with combination therapy appeared to suffer more severe IRAEs producing more substantial long-term morbidity and mortality. In this clinical practice study, the incidence of neurologic IRAEs from ICIs was 0.95%. Although rare, neurologic IRAEs can be highly variable and severe, and patients with combination immunotherapy appeared to suffer more severe IRAEs. Neurologists play an important role in the early identification and management of IRAEs to reduce long-term morbidity and mortality.

Spinobulbar muscular atrophy combined with atypical hereditary neuropathy with liability to pressure palsy

Spinobulbar muscular atrophy (SBMA) is an X-linked recessive disease, presenting motor weakness and wasting of facial, bulbar and limb muscles. Hereditary neuropathy with liability to pressure palsy (HNPP) is autosomal dominant disorder characterized by recurrent neuropathies at common entrapment sites. We report a case of co-existence of SBMA and atypical HNPP with genetic confirmation of CAG expansion in the androgen receptor (AR) gene and deletion of the peripheral myelin protein 22 (PMP22) gene. A 62-year-old man presented with progressive muscle weakness, fasciculations in upper and lower limbs and dysesthesia predominantly in the distal regions. No family members, including his children, experienced similar symptoms. The electrodiagnostic examination was compatible with demyelinating sensorimotor polyneuropathy. Simultaneous hereditary polyneuropathy and motor neuron disease were suspected and relevant genetic testing was confirmed HNPP and SBMA. This case presented with 2 rare genetic neuromuscular disorders and the atypical HNPP phenotype. This case highlight the importance of detailed patient histories, as well as neurological and electrophysiological examinations for diagnosis of atypical and combination of rare genetic disorders.

Atypical Features in a Large Turkish Family Affected with Friedreich Ataxia.

Here, we describe the clinical features of several members of the same family diagnosed with Friedreich ataxia (FRDA) and cerebral lesions, demyelinating neuropathy, and late-age onset without a significant cardiac involvement and presenting with similar symptoms, although genetic testing was negative for the GAA repeat expansion in one patient of the family. The GAA repeat expansion in the frataxin gene was shown in all of the family members except in a young female patient. MRI revealed arachnoid cysts in two patients; MRI was consistent with both cavum septum pellucidum-cavum vergae and nodular signal intensity increase in one patient. EMG showed demyelinating sensorimotor polyneuropathy in another patient. The GAA expansion-negative 11-year-old female patient had mental-motor retardation, epilepsy, and ataxia. None of the patients had significant cardiac symptoms. Description of FRDA families with different ethnic backgrounds may assist in identifying possible phenotypic and genetic features of the disease. Furthermore, the genetic heterogeneity observed in this family draws attention to the difficulty of genetic counseling in an inbred population and to the need for genotyping all affected members before delivering comprehensive genetic counseling.

Late infantile metachromatic leukodystrophy presenting with extrapyramidal sign

Metachromatic leukodystrophy (MLD) is a progressive white matter disease caused by arylsulfatase A deficiency. Demyelination in the nervous system is detected by cerebral magnetic resonance imaging and neurophysiological studies. We present here a child with late infantile MLD, who had initially difficulties in standing and walking with generalized dystonia and clubfoot and later on became unable to stand and sit even with support. Protein levels in cerebral spinal fluid were elevated and nerve conduction studies revealed slowing down of motor and sensory nerve conduction velocity. Initial cerebral computerized tomography scan showed hypo dense lesion in bilateral globus pallidus. Magnetic resonance imaging was done subsequently that showed diffuse white matter signal changes. Enzyme assay for arylsulfatase A further confirmed the diagnosis of MLD. We conclude that in young children extrapyramidal symptomatology and demyelinating sensorimotor polyneuropathy may be a presenting feature of the onset of MLD.

Beneficial effects of Rituximab in patients with anti-MAG (myelin-associated glycoprotein) neuropathy: case reports

Anti-myelin-associated glycoprotein (MAG) neuropathy is a primary demyelinating sensorimotor polyneuropathy that can be very debilitating and is known to be resistant to treatment. There are only a few conflicting reports on the effect of Rituximab in anti-MAG neuropathy. We present three patients who improved remarkably with Rituximab infusions. Until the safety and efficacy of this drug are determined in larger controlled studies, use of Rituximab should be limited to patients with significant neurologic deficits.

Trichloropropane and dichlorohydrin associated with painful peripheral neurotoxicity

Trichloropropane (TCP) and dichlorohydrin are widely used in industrial production; however, TCP and dichlorohydrin poisoning are rarely encountered in clinical practice. There have been no cases of peripheral neurotoxicity previously reported. A cluster of 23 patients who had been exposed to high levels of TCP and dichlorohydrin presented with painful peripheral neuropathy, and the pain was assessed using a visual analogue scale (VAS). Nerve conduction studies (NCS) were performed in all patients. All patients demonstrated symmetrical pin-prick pain in a stocking distribution in the lower limbs, with VAS scores between 3 and 10, with an average score of 6.8. NCS showed a mild mixture of axonal and demyelinating sensorimotor polyneuropathy in 14 of the 23 patients. After administration of standard neuropathic pain medication, pain was relieved in most patients. Painful peripheral neuropathy was the primary symptom observed in our patients, which differs from clinical and animal model reports of TCP or dichlorohydrin poisoning. However, the pathogenesis remains unidentified. TCP may be added to the list of industrial products that are toxic to the peripheral sensory nerves.

Knee MRI showing thickened peripheral nerves in Charcot–Marie–Tooth disease

A 16-year-old boy with 3-year history of knee pain was initially seen in the orthopedic clinic. He was then referred to the pediatric neurology clinic after an abnormal magnetic resonance imaging (MRI) of the knee (Figs. 1, 2). Axial and sagittal T2 weighted with fat suppressed MRI images obtained at the level of midline patella demonstrated diffuse enlargement of the sciatic (solid arrow) and tibial (dotted arrow) nerves with increased signal intensity. The knee joint was normal on MRI. On examination, the significant clinical findings were thoracic scoliosis, pes cavus, weakness of ankle and toe dorsiflexors, generalized areflexia, distal sensory loss in the legs and thickened peripheral nerves. The family history was negative for any neuromuscular disease or foot deformities. Electrodiagnostic studies were consistent with hereditary demyelinating sensorimotor polyneuropathy. DNA analysis identified the duplication of peripheral myelin protein 22 (PMP22) gene on chromosome 17. This confirmed the diagnosis of Charcot–Marie–Tooth (CMT) type 1A disease. CMT is a genetically heterogeneous group of inherited neuropathies with variable age of presentation [1]. The typical clinical presentation is that of slowly progressive distal lower extremity weakness and peroneal muscles atrophy with characteristic foot abnormalities (pes cavus, hammer toes), followed by weakness and atrophy of upper extremity muscles and sensory loss [2]. Genetically CMT type 1A is the most common form and is associated with 1.4 Mb duplication at chromosome 17p11.2 [1]. The family history may be negative in autosomal recessive or potentially new dominant mutations as noted in our case. In our patient the clinical features, electrodiagnostic studies and genetic studies confirmed CMT type 1A. However, the patient’s presentation with knee pain was atypical. We think that the knee pain was secondary to the foot deformities and muscle weakness due to CMT.

Hip dysplasia associated with a hereditary sensorimotor polyneuropathy mimics a myopathic process

Some orthopedic complications have been reported in the hereditary neuropathies. However, the association of the hip dysplasia with this category of neuropathy is rarely recognized. We present a 13-year-old boy with the progressive weakness of the lower extremities, difficulty in walking, climbing stairs, and rising from floor; a wide-based, hyper-extended and waddling gait similar to a myopathic process. Hip radiography showed dysplastic acetabulae with hip subluxation, broken Shenton's lines, and valgus femoral necks. In electrodiagnosis, there was a significant neuropathic process (absent all evoked sensory potentials, abnormal evoked motor responses, and neurogenic electeromyography) which eventually was found to be a hereditary mixed axonal and demyelinating sensorimotor polyneuropathy with concomitant hip dysplasia confirmed with thorough physical examination and the electrodiagnostic study. In patients with gait difficulties such as waddling gait mimicking a myopathic process, hereditary polyneuropathy complicated with hip dysplasia should be considered as well.