Optic Neuropathy and Myelopathy in a Teenager With Biotinidase Deficiency.

ABSTRACT: A 19-year-old man presented with 3 years of gradually progressive, painless vision loss in both eyes. The ophthalmic examination showed bilateral diminished visual acuity, dyschromatopsia, and temporal optic nerve pallor. The neurological examination was consistent with a mild myelopathy with decreased pin-prick sensation starting at T6-T7 and descending through the lower extremities. Hyperreflexia was also present in the lower more than upper extremities. Infectious, inflammatory, and nutritional serum workup and cerebrospinal fluid analysis were both unrevealing. MRI of the brain and spinal cord showed abnormal T2 hyperintensity of the fornix, corpus callosum, optic nerves, and lateral columns of the cervical and thoracic spine, with diffusion restriction in the inferior-posterior corpus callosum and fornix. Biotinidase serum enzyme activity was tested and showed a decreased level of activity. Biotinidase gene testing showed a homozygous pathogenic variant, c.424C>A (p.P142T), confirming the diagnosis of biotinidase deficiency and prompting oral biotin supplementation. Three months after starting treatment, the patient's visual acuity, color vision, visual fields, and MRI spine abnormalities all improved significantly. Biotinidase deficiency is an important diagnostic consideration in patients with unexplained optic neuropathy and/or myelopathy.

[Clinical guidelines for diagnosis and treatment of cervical spondylotic myelopathy with the integrated traditional Chinese and Western medicine(2023)].

The "Clinical Guidelines for Diagnosis and Treatment of Cervical Spondylotic Myelopathy with the Integrated Traditional Chinese and Western Medicine" were formulated by the Orthopedic and Traumatology Professional Committee of the Chinese Association of Integrative Medicine in accordance with the principles of evidence-based medicine and expert consensus, and provide clinicians with academic guidance on clinical diagnosis and treatment of CSM. The main content includes diagnostic points, disease grading assessment, TCM syndrome differentiation, surgical indications and timing, integrated traditional Chinese and Western medicine treatment, and postoperative rehabilitation. This guideline proposes for the first time that the treatment of CSM should follow the principle of grading, clarify the timing and methods of surgical treatment, establish common TCM syndrome differentiation and classification, attach importance to postoperative integrated rehabilitation of Chinese and Western medicine, and strengthen daily follow-up management. It hopes to promote the standardization, effectiveness, and safety of clinical treatment of CSM.

[Cervical myelopathy due to copper deficiency secondary to dental zinc overload: A case report]. / Mielopatía cervical por déficit de cobre secundario a sobrecarga de zinc dental. A propósito de un caso.

We present the case of a 68-year-old man with progressive brachial and crural hypoaesthesia with gait ataxia suggesting subacute myelopathy of the posterior cords, demonstrated by MRI. After blood tests, a diagnosis of copper deficiency was made following zinc intoxication, secondary to the use of denture glue containing zinc. Treatment was started with copper and the dental glue was removed. Rehabilitation treatment was started with physiotherapy, hydrotherapy and occupational therapy. Functional improvement was achieved, going from an ASIAD level C4 to an ASIAD level C7 spinal cord injury. Copper levels should be studied in all non-compressive myelopathies of subacute onset if there is clear involvement of the posterior cords. Copper deficiency in analysis would establish the diagnosis. Rehabilitative treatment, supplementary copper supplementation and zinc withdrawal are essential to prevent irreversible neurological damage.

[Expert consensus for diagnosis and treatment of cervical spondylotic myelopathy with the integrated traditional Chinese and western medicine].

Cervical spondylotic myelopathy (CSM) is the most serious subtype, which is characterized by severe clinical symptoms, a high disability rate, and poor prognosis. Traditional Chinese medicine and Western medicine have their own advantages in the diagnosis and treatment of CSM at different stages. In order to further standardize the clinical diagnosis and treatment of CSM and improve the clinical efficacy, based on previous experience and evidence-based medicine, after repeated discussions by the national expert group, the expert consensus on the diagnosis and treatment of integrated traditional Chinese and Western medicine was compiled. This consensus comprehensively introduces the definition, etiology, pathogenesis, diagnosis treatment principles, integrated traditional Chinese and Western medicine treatment, postoperative rehabilitation and nursing care of cervical spondylotic myelopathy, so as to provide reference for clinicians.

Recognition of prodromal cervical spondylotic myelopathy presenting in a U.S. Veteran referred to chiropractic for acute thoracic pain: A case report.

OBJECTIVE: To highlight a patient who was referred to a VA chiropractic clinic for thoracic pain and upon physical exam was found to be myelopathic, subsequently requiring surgery. CLINICAL FEATURES: A 58-year-old male attended a telephone interview with the VA chiropractic clinic for thoracic pain of 4 months duration; he denied neck pain, upper extremity symptoms or clumsiness of the feet or hands. At his in-person visit, he acknowledged frequently dropping items. The physical examination revealed signs of myelopathy including positive Hoffman's bilaterally, 3+ brisk patellar reflexes, and 5+ beats of ankle clonus bilaterally. He also had difficulty walking heel/toe. INTERVENTION AND OUTCOME: Cervical and thoracic radiographs were ordered and a referral was placed to the Physical Medicine and Rehabilitation (PM&R) Clinic for evaluation of the abnormal neurologic exam and suspicion of cervical spondylotic myelopathy (CSM). He was treated for 2 visits in the chiropractic clinic for his thoracic pain, with resolution of thoracic symptoms. No treatment was rendered to the cervical spine. The PM&R physician ordered a cervical MRI which demonstrated severe central canal stenosis and increased T2 signal within the cord at C5-C6, representing myelopathic changes. The PM&R specialist referred him to Neurosurgery which resulted in a C5-6, C6-7 anterior cervical discectomy and fusion. CONCLUSION: The importance of physical examination competency and routine thoroughness cannot be overstated. Swift identification of pathologic signs by the treating chiropractor resulted in timely imaging and surgical intervention.

Metabolic and Toxic Myelopathies.

PURPOSE OF REVIEW: This article describes the clinical presentation, relevant diagnostic investigations, and treatment of metabolic and toxic myelopathies. RECENT FINDINGS: Metabolic myelopathies, including those due to deficiency of vitamin B12, folate, copper, or vitamin E, are preventable and typically respond to supplementation. In metabolic myelopathy, early recognition and treatment are important to reduce morbidity, particularly due to subacute combined degeneration of the spinal cord. Toxic myelopathies, including those due to medical interventions (eg, methotrexate, radiation), dietary toxins (eg, lathyrism, konzo), and drugs of abuse (eg, heroin), typically result in permanent neurologic deficits. Toxic myelopathy due to hepatic dysfunction may be reversible if patients receive early intervention, whereas nitrous oxide myelopathy responds to vitamin B12 replacement and cessation of exposure. In toxic myelopathy, it is best to avoid the provoking factor when possible or attempt to mitigate risk by identifying risk factors for developing myelopathy. SUMMARY: Metabolic and toxic myelopathies are important causes of morbidity that require a high index of suspicion for diagnosis.

Zinc containing dental fixative causing copper deficiency myelopathy.

A 62-year-old male, previously well, was referred to neurology clinic following 6 months history of worsening lower limbs instability, paraesthesia, pain and weakness rendering him housebound. Examination revealed upper motor neuron pattern of weakness of the lower limbs and loss of proprioception. Serum analysis revealed reduced caeruloplasmin and copper levels with raised zinc. Spinal imaging revealed subtle dorsal column intensity changes in C2-C7, confirmed with 3T MRI. A copper deficiency myeloneuropathy was diagnosed secondary to chronic use of a zinc-containing dental fixative paste. The paste was discontinued and a copper supplementation was started. Resolution of symptoms was not achieved with intensive physiotherapy. The patient remains a wheelchair user though progression of symptoms has halted. Prompt recognition and treatment of hyperzincaemia-induced hypocupraemia earlier in the disease course may have prevented any irreversible neurological deficit.

Subacute copper-deficiency myelopathy in a patient with occult celiac disease.

CONTEXT: Acquired copper deficiency represents a rare cause of progressive myelopathy presenting with sensory ataxia and spastic gait. The time interval from neurological symptoms onset to diagnosis of myelopathy ranges from 2 months to several years in almost all cases, mimicking the clinical course of subacute combined degeneration due to vitamin B12 deficiency. FINDINGS: A 60-year-old man, without any gastrointestinal symptoms, developed over the course of one week rapidly progressive gait imbalance, tingling and numbness in his feet and ascending lower limb weakness. Spine magnetic resonance imaging revealed hyperintensity involving cervical and dorsal posterior columns of spinal cord. Blood analysis revealed undetectable serum copper levels, low serum ceruloplasmin and positive serum Immunoglobulin A anti-tissue transglutaminase. Upper gastrointestinal endoscopy was performed revealing duodenal villous atrophy consistent with a malabsorption pattern. A gluten-free diet in association with intravenous then oral copper supplementation prompted sustained normalization of serum copper levels and progressive clinical improvement. CONCLUSION/CLINICAL RELEVANCE: We report a rare case of myelopathy induced by copper deficiency secondary to undiagnosed celiac disease, peculiarly presenting with a subacute onset. This case expands the neurological presentation and clinical course of myelopathy due to acquired copper deficiency. We suggest investigation of copper deficiency in patients presenting with subacute or even acute sensory ataxia and spastic gait. Detection of hypocupremia in patients without a previous history of gastric surgery should lead to diagnostic testing for celiac disease even in the absence of any obvious gastrointestinal symptoms.

Maple Syrup Urine Disease Complicated with Kyphoscoliosis and Myelopathy.

Maple syrup urine disease (MSUD) is an autosomal recessive aminoacidopathy secondary to an enzyme defect in the catabolic pathway of the branched-chain amino acids (BCAAs: leucine, isoleucine, and valine). Accumulation of their corresponding keto-acids leads to encephalopathy if not treated in time. A newborn male patient was suspected to have MSUD after tandem mass study when he presented symptoms and signs suggestive neonatal sepsis, anemia, and diarrhea. Food restriction of BCAAs was started; however, acrodermatitis enteropathica-like skin eruptions occurred at age 2 months. The skin rashes resolved after adding BCAAs and adjusting the infant formula. At age 7 months, he suffered from recurrent skin lesions, zinc deficiency, osteoporosis, and kyphosis of the thoracic spine with acute angulation over the T11-T12 level associated with spinal compression and myelopathy. After supplementation of zinc products and pamidronate, skin lesions and osteopenia improved gradually. Direct sequencing of the DBT gene showed a compound heterozygous mutation [4.7 kb deletion and c.650-651insT (L217F or L217fsX223)]. It is unusual that neurodegeneration still developed in this patient despite diet restriction. Additionally, brain and spinal magnetic resonance imaging, bone mineral density study, and monitoring of zinc status are suggested in MSUD patients.

Copper deficiency myelopathy: A report of two cases.

CONTEXT: Copper deficiency myelopathy represents an often underdiagnosed, acquired neurological syndrome, clinically characterized by posterior column dysfunction. The main causes of copper deficiency are bariatric surgery, increased consumption of zinc, and malabsorption. However, even after a careful history taking and extensive laboratory researches, the etiology of copper deficiency remains undetermined in a significant percentage of cases. Patients affected by copper deficiency myelopathy usually present with sensory ataxia due to dorsal column dysfunction and sometimes with mild leg spasticity. In such patients, spinal cord magnetic resonance imaging (MRI) may show hyperintense lesions in T2-weighted sequences involving the posterior columns of cervical and thoracic cord. These MRI findings are not distinguishable from those of subacute combined degeneration associated with vitamin B12 deficiency. FINDINGS: Here, we describe two patients with gait ataxia and sensory symptoms in which a diagnosis of copper deficiency myelopathy was made. Both patients showed a significant clinical, neuroradiological, and neurophysiological improvement after proper supplementation therapy. CONCLUSION: The patients herein described underline the importance to include serum copper and ceruloplasmin levels as part of the myelopathy diagnostic workup, especially in the cases of otherwise unexplained subacute myelopathy involving the posterior columns. Since copper deficiency myelopathy is a progressive syndrome, early diagnosis is mandatory in order to promptly provide a proper supplementation therapy and, thus, prevent an irreversible neurological damage.

Optic neuropathy, myelopathy, anemia, and neutropenia caused by acquired copper deficiency after gastric bypass surgery.

Malabsorptive bariatric surgery is rapidly becoming a major cause of copper deficiency given the increasing prevalence of these procedures for morbid obesity. Acquired copper deficiency can present with clinically significant hematologic and neurological manifestations. Although hematologic manifestations of copper deficiency are rapidly reversible, significant neurological improvement after copper supplementation therapy is unusual and many patients remain debilitated and may only experience, at best, stabilization of the neurological manifestations. Here we present a case of an undiagnosed copper deficiency several years after bariatric gastric bypass surgery, in a patient who concomitantly used zinc-containing denture cream for several years, associated with anemia, neutropenia, myelopathy, respiratory failure, and bilateral optic neuropathy, which caused major vision loss. This patient was also a heterozygote carrier of the 5,10-methylenetetrahydrofolate reductase A1298C gene polymorphism, which may affect copper metabolism. Intravenous copper repletion resulted in rapid correction of hematologic indices. However, neurological manifestations, including vision loss responded only modestly to copper supplementation, despite achieving normal blood copper concentrations. Clinicians should consider copper deficiency in patients at risk, as in this case, as a delayed diagnosis can lead to irreversible disability due to neurological manifestations.

Nitrous oxide induced myeloneuropathy: a case report.

We report the case of a 35-year-old male with a history of chronic, escalating nitrous oxide abuse who presented to the ER with a history of recent onset generalized weakness, altered sensorium, abnormal posturing of the hands, urinary complaints, and decreased balance. Physical examination was notable for pathologically brisk reflexes in all extremities, generalized flexion contracture of the fingers, decreased sensation in a stocking and glove distribution, and a weakly positive Babinski sign. The patient was noted to be a poor historian with decreased attention and concentration though otherwise generally alert and oriented. No discrete sensory level in the chest or trunk was detected, and the overall clinical appearance was felt to be most compatible with a mixed myeloneuropathic pattern of central and peripheral involvement. Laboratory findings were normal and noncontributory. Cervical spine MRI subsequently performed to rule out cord compression, intrinsic spinal cord mass, or demyelinating disease was notable for a long segment of increased T2 signal extending from C2-C3 to C6-C7 localizing to the dorsal columns of the cord in a typical "inverted V" fashion. No associated cord expansion was seen nor was there evidence of extrinsic compression; faint associated contrast enhancement was observed on post-gadolinium images. Further evaluation with nerve conduction velocity and electromyographic testing was deferred. Based on the exam findings, clinical history, and presentation, a diagnosis of nitrous oxide-related myeloneuropathy was made, and treatment with high-dose vitamin B12 supplementation was instituted. Recovery has been slow to date.

Slowly progressive folate-deficiency myelopathy: report of a case.

BACKGROUND: Folate deficiency is known to be associated with subacute combined degeneration of the spinal cord; however, reports of long-standing cases are rare. Although neurological deficits due to folate deficiency have been reported to respond to folic acid supplementation, the functional outcomes have not been fully elucidated. OBJECTIVE: The aim of the study was to evaluate the clinical features and response to folate supplementation in a patient with folate deficiency manifested over 10 years as a slowly progressive myelopathy. METHODS: We performed comprehensive clinical screening, electrophysiological testing, and posturography before and after folate supplementation. RESULTS: A 49-year-old man had a slowly progressive gait disturbance for 10 years. He had not eaten fresh green vegetables for more than 10 years. Neurological examination revealed spastic paraplegia and absence of any vibration sense in the lower limbs accompanied by a positive Romberg's sign. Serum folate level was low, and plasma homocysteine level was elevated. Levels of blood thiamine and serum cobalamin were normal. We diagnosed the patient with myelopathy due to folate deficiency. Folic acid supplementation led to improvement of his symptoms; posturography and walking speed tests showed partial improvement, while the somatosensory-evoked potentials and central motor conduction time remained unchanged. CONCLUSIONS: Folate deficiency should be considered as a differential diagnosis of chronic slowly progressive myelopathy. The present case suggests the importance of early diagnosis and treatment before the adverse neurological manifestations of folate deficiency become irreversible.

MRI findings in cervical spinal cord type II neurological decompression sickness: a case report.

Decompression illness affecting the cervical spinal cord is uncommon. We report a case that presented with mixed signs and symptoms of cervical myelopathy and Type II neurological decompression sickness. This presented a diagnostic dilemma that required the use of magnetic resonance imaging (MRI) scan to elucidate the underlying cause. Cervical spine MRI revealed the presence of tiny hypointensities and edema within the spinal cord that corresponded to the clinical findings. The patient recovered with residual neurological deficits after hy-perbaric oxygen (HBO2) therapy. To our knowledge, these MRI findings have yet to been described in literature and we recommend the use of MRI to assist diving physicians in the management of complex cases as long as it does not delay recompression.

Intravesical electrostimulation versus sacral neuromodulation for incomplete spinal cord patients suffering from neurogenic non-obstructive urinary retention.

OBJECTIVES: To compare the efficacy of intravesical electrostimulation (IVES) versus sacral neuromodulation (SNM) in patients with incomplete spinal cord lesions (SCL) and neurogenic non-obstructive urinary retention (N-NOR). METHODS: In this retrospective study, 77 N-NOR patients underwent IVES (minimum 28 sessions), then after returning to voiding baseline symptoms, percutaneous first stage of SNM (lasting for minimum 4 weeks). After the two neuromodulation treatments, responders were categorized as patients experiencing both a 50% reduction of volume per catheterization per ml and a 50% reduction in number of catheterizations per day when comparing the 7-day voiding diaries at the end of both procedures to baselines. New urodynamics were performed subsequently. Responders to first stage of SNM underwent permanent SNM. RESULTS: Forty-eight patients responded to neither of the treatments, whereas 29 responded to both IVES and first-stage SNM. No significant statistical differences (P>0.05) were detected in the voiding diaries. Following the two procedures, the first sensation of bladder filling was either maintained or recovered by all responders, whereas the same 11 patients reached a bladder contractility index of >100. The 29 IVES responders lost their clinical benefits in a mean follow-up of 9.6 months. Only 10 out of the 29 patients became nonresponsive to permanent SNM, in a mean follow-up of 54 months. CONCLUSION: A strict correlation in terms of clinical and urodynamic patterns was demonstrated in patients with incomplete SCL and N-NOR, following IVES and first stage of SNM. However, voiding improvement through IVES was short-term when compared with the effects of permanent SNM.

Secondary degeneration detected by combining voxel-based morphometry and tract-based spatial statistics in subcortical strokes with different outcomes in hand function.

BACKGROUND AND PURPOSE: Secondary degeneration of the pyramidal tract after focal motor pathway stroke has been observed by diffusion tensor imaging. However, the relationships between outcomes in hand function and secondary degeneration in widespread regions are not well understood. For the first time, we investigated the differences of secondary degeneration across the whole brain between subgroups of patients with stroke. MATERIALS AND METHODS: We selected 23 patients who had a subcortical stroke in the left motor pathway and displayed only motor deficits. The patients were divided into 2 subgroups: CPH (11 patients) and PPH (12 patients). Twelve healthy controls matched for age and handedness were also recruited. We used both optimized VBM and TBSS to explore differences of FA across the whole brain between CPH and PPH. Furthermore, ROI analysis was carried out in the identified regions detected by VBM analysis to further quantify the degree of secondary degeneration in the CPH and PPH and compare these with healthy controls. RESULTS: Compared with PPH, FA was significantly decreased in the CPH in widespread regions of the motor system remote from the primary lesion, including the ipsilesional brain stem, medial frontal gyrus, precentral gyrus, superior temporal gyrus, supplementary motor area, and contralesional postcentral gyrus. In addition, FA within these identified regions correlated with Fugl-Meyer Assessment scores (hand+wrist). CONCLUSIONS: This study suggests a potential biomarker for outcome differences in hand function after subcortical stroke.

Myelopathy secondary to copper deficiency as a complication of treatment of Wilson's disease.

Wilson's Disease (WD) is an autosomal recessive disorder of copper metabolism resulting in a pathological accumulation of this metal, initially in the liver and later in other organs, mainly brain. Treatment with copper chelating agents and zinc salts results in a depletion of copper deposits and prevents or reverses the clinical manifestations. Copper deficiency may cause haematological and neurological changes, the latter principally being polyneuropathy and myelopathy. We report a patient with WD who developed a myelopathy associated with a deficiency of copper following prolonged treatment with D-penicillamine and zinc salts.

Clinical tests for screening and diagnosis of cervical spine myelopathy: a systematic review.

OBJECTIVE: The purpose of this review was to investigate the diagnostic accuracy for screening and confirmation of clinical tests for cervical spine myelopathy (CSM) and to investigate the quality of the studies that have investigated these values. METHODS: This study was a systematic review that used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Search terms for PubMed included myelopathy; diagnosis, differential; sensitivity and specificity; and physical examination. Search terms for Cumulative Index to Nursing and Allied Health Literature were limited to myelopathy and sensitivity and specificity. Qualitative assessment included report of diagnostic accuracy metrics (sensitivity, specificity, and positive and negative likelihood ratios) and quality scores using the Quality Assessment of Diagnostic Accuracy Studies tool. Scores were created for single tests and clustered test findings. RESULTS: After evaluation, 12 full-text articles were selected, scored, and tabulated. Nearly all of the 18 tests demonstrated high levels of specificity and low levels of sensitivity, suggesting that they are poor screening tools. Only one study was scored as high quality. One study involved clustering of test findings but was considered low quality. CONCLUSION: Nearly all of the clinical tests for CSM seem to be poor screening tools, which implies that manually oriented clinicians may perform treatment methods in a situation of doubt or uncertainly. More high-quality studies are needed, and manual therapists need to be cognizant that the current clinical tests for CSM lack strong diagnostic accuracy measures that are necessary for clinical decision making.

Prognostic factors of spinal cord decompression sickness in recreational diving: retrospective and multicentric analysis of 279 cases.

BACKGROUND: This study aims to determine the potential risk factors associated with the development of severe diving-related spinal cord decompression sickness (DCS). METHODS: Two hundred and seventy nine injured recreational divers (42 ± 12 years; 53 women) presenting symptoms of spinal cord DCS were retrospectively included from seven hyperbaric centers in France and Belgium. Diving information, symptom latency after surfacing, time interval between symptom onset and hyperbaric treatment were studied. The initial severity of spinal cord DCS was rated with the Boussuges severity score, and the presence of sequelae was evaluated at 1 month. Initial recompression treatment at 2.8 ATA with 100% oxygen breathing or deeper recompression up to 4 or 6 ATA with nitrogen or helium-oxygen breathing mixture were also recorded. RESULTS: Twenty six percent of DCS had incomplete resolution after 1 month. Multivariate analysis revealed several independent factors associated with a bad recovery: age ≥ 42 [OR 1.04 (1-1.07)], depth ≥ 39 m [OR 1.04 (1-1.07)], bladder dysfunction [OR 3.8 (1.3-11.15)], persistence or worsening of clinical symptoms before recompression [OR 2.07 (1.23-3.48)], and a Boussuges severity score >7 [OR 1.16 (1.03-1.31)]. However, the time to recompression and the choice of initial hyperbaric procedure did not significantly influence recovery after statistical adjustment. CONCLUSIONS: Clinical symptoms of spinal cord DCS and their initial course before admission to the hyperbaric center should be considered as major prognostic factors in recovery. A new severity score is proposed to optimize the initial clinical evaluation for spinal cord DCS.

Reversible myelopathy with vitamin B12 deficiency.

Vitamin B12 deficiency causes haematological, gastrointestinal, psychiatric and neurological diseases. Subacute combined degeneration (SCD) of the spinal cord, characterised by degeneration of the lateral and posterior columns, is often found due to vitamin B12 deficiency. We report SCD occurring in a 57-year-old man who presented with a 2.5-month history of gradually progressing tingling in the fingers and toes and neck ache. Laboratory data revealed vitamin B12 deficiency and magnetic resonance (MR) imaging of the cervical spinal cord demonstrated abnormal hyperintense signal changes on T2-weighted imaging of the posterior columns. In our case, follow-up MR imaging findings correlated well with clinical outcome after treatment with vitamin B12 supplements. Neurological symptoms in vitamin B12 deficiency are frequent. Early spinal MR imaging assists in the early diagnosis and treatment of the disease.