Subacute Combined Degeneration Research Articles

Adrenomyeloneuropathy in a subacute combined degeneration suspect: a diagnostic dilemma

Adrenomyeloneuropathy (AMN) is a variant of adrenoleukodystrophy (ALD) which is a peroxisomal disorder of beta-oxidation that results in accumulation of very long-chain fatty acids (VLCFAs) in plasma, central and peripheral nervous systems, adrenal glands and testes leading to their dysfunction. These conditions are known as the ALD/AMN complex. In this article we discuss a case of AMN with respect to clinical presentation, diagnosis and treatment.

V for vitamin, inverted V for lack of it: A rare case of subacute combined degeneration of cord with bladder symptoms and associated multiple Tarlov cysts

Subacute degeneration of cord (SACD) is a rare presentation of a common disease and it should be kept in mind when the patient develops symptoms of peripheral neuropathy. This is a case of a 65-year-old male who presented with pins and needles sensation of bilateral hands and feet and with difficulty in voiding. Neurological examination showed large fiber neuropathy with an exaggerated knee jerk, absent ankle jerk, extensor plantar, and a positive Romberg’s sign. Routine laboratory investigations showed low hemoglobin and low vitamin B12 levels. Magnetic resonance imaging of the spinal cord showed a hyperintense lesion in the posterior aspect of the cervical cord with a classical “inverted V” sign on the axial section which is suggestive of SACD. Coincidentally, there were multiple Tarlov cysts present. Finally, the patient improved with vitamin B12 injections. This case is unique as an association of SACD with Tarlov cysts with a classical inverted V sign has not been reported according to the literature.

Lichtheim disease: A rare manifestation of pernicious anemia

Subacute combined degeneration of the spinal cord (SACD) is an important neurological complication of vitamin B12 deficiency. It is an important treatable cause of progressive neurological disability. We report a case of a 12-year-old girl, which presented with features of SACD of the spinal cord with low vitamin B12 levels and positive anti-parietal cell antibodies, suggesting vitamin B12 deficiency due to autoimmune etiology. The girl was started on a regimen of intramuscular vitamin B12 treatment. After which she had complete neurological recovery. She was advised of lifelong supplementation of parenteral vitamin B12 due to the autoimmune etiology.

110 Methylmalonic acid testing in neurological patients

Vitamin B12 deficiency can lead to neurological abnormalities including paraesthesia, ataxia and subacute combined degeneration of the cord (SACD). Nitrous oxide abuse leads to SACD via func- tional B12 deficiency. Methylmalonic acid (MMA) testing is increasingly available, but it remains unclear where MMA levels are clinically useful.We performed a quality improvement project examining Vitamin B12 and MMA levels in a cohort of neu- rological patients. All patients known to neurology who underwent same-day testing of B12 and MMA levels (2016–2019) were included.60 individual patient records were evaluated. 17 individuals (28%) had high MMA, of whom 6 individuals had SACD and 11 had peripheral neuropathy. These patients had B12 levels between 91–371ng/L (lower limit of normal (LLN) is 197ng/L). Of these, only one had severe B12 deficiency, 4 had moderate deficiency (150–197ng/L) and 12 (71%) had normal B12. The highest B12 level associated with raised MMA was 372ng/L. All individuals with B12 >372ng/L and neurological symptoms had normal MMA.In individuals with serum vitamin B12 above the lower 1/3 of the reference range and neurological symptoms/signs, MMA does not add to the clinical picture. Furthermore, MMA testing does not change management in patients with B12 levels below the LLN, all of whom should be treated for B12 deficiency. We suggest testing MMA in those with Vitamin B12 levels in the lower 1/3 of the reference range.katieyoganathan@gmail.com

Falsely “high” serum cobalamin level in subacute combined degeneration of spinal cord secondary to pernicious anemia masquerading as myelodysplastic syndrome

AbstractCobalamin deficiency causes clinical manifestations ranging from anemia to neuropsychiatric presentations. We present a patient initially treated as myelodysplastic syndrome (MDS), who was later diagnosed to have pernicious anemia. He presented with pancytopenia, and bone marrow aspirate was suggestive of MDS. Serum cobalamin was high. Six months later, he developed progressive lower limb weakness. Magnetic resonance imaging (MRI) of the spine showed a hyperintense signal in the lateral aspects of the cord at C6 to T10 suggestive of subacute combined degeneration of the spinal cord. Homocysteine, methylmalonic acid, and anti‐intrinsic factor levels were found to be high, confirming the diagnosis of cobalamin deficiency secondary to pernicious anemia. His pancytopenia and weakness improved markedly after 5 months of parenteral cobalamin injection. This case highlights that cobalamin deficiency can mimic MDS, and second‐line assays are important in a patient with a high clinical suspicion of cobalamin deficiency despite normal serum cobalamin level.

Just 'nanging' around - harmful nitrous oxide use: a retrospective case series and review of Internet searches, social media posts and the coroner's database.

The chronic recreational inhalation of nitrous oxide (N2 O) 'nanging', can have adverse neurological and psychiatric effects. To evaluate cases of chronic N2 O use presenting to two hospitals, as well as to evaluate nationally N2 O deaths reported to the coroner and trends in Internet searches and social media posts related to N2 O. Retrospective review of two toxicology units, from July 2017 to October 2020, of patients presenting with chronic N2 O use and neurological and/or psychiatric symptoms. We evaluated 10 years (2010-2019) of Internet search and social media trends involving N2 O and the National Coronial Information System (NCIS) database for deaths across Australia. Twenty-two patients were identified: median age 22 years, half female, 17 Asian background and 15 students. Presentations included decreased mobility or unsteady gait (n = 15) and psychiatric symptoms (n = 5). The median reported bulb use/day was 300 (interquartile range (IQR): 200-370), for a median of 6 months (IQR: 3-24). On magnetic resonance imaging, 10/18 had subacute combined degeneration of the spinal cord and 7/7 sensorimotor neuropathy on nerve conduction studies. All received high-dose intramuscular vitamin B12 and 11 methionine. Despite prolonged rehabilitation, nine required walking aids on discharge. Since 2017, social media posts and Internet searches for N2 O increased rapidly, the latter mostly directed at obtaining N2 O canisters. From the NCIS, 36 deaths were identified, 12 unintentional (recreational drug use), 20 intentional self-harm and 4 traumatic. We report a case series of symptomatic chronic N2 O use, many with ongoing neurological sequelae. Furthermore, a sharp increase in Internet searches to obtain N2 O cannisters was noted. Education of high-risk student groups on the long-term sequelae is important.

Nitrous Oxide Induced Subacute Combined Degeneration (SCD) of Spinal Cord. (P7-12.004)

Nitrous Oxide Induced Subacute Combined Degeneration (SCD) of Spinal Cord. (P7-12.004)

Nitrous oxide‐induced neurological disorders: an increasing public health concern

Neurological presentations resulting from nitrous oxide (N2 O) abuse are increasing in Australia and worldwide. Despite known neuropsychiatric sequelae, N2 O canisters remain readily available and its use unregulated. To examine the demographics, clinical and electrophysiological findings of patients presenting with neurological complications of N2 O abuse, and thus inform clinicians and public health decision-makers of the significant public health concerns of this increasing practice. Consecutive patients presenting to a tertiary referral metropolitan hospital were included in this series. Patients were identified by a search of discharge summaries of patients admitted with acute or subacute neuropathy or myelopathy and a history of N2 O abuse, and from the electrophysiology database. Thirteen patients were identified, most presenting with subacute paraesthesia, sensory ataxia and lower limb weakness. Eleven had low serum vitamin B12 . Spinal magnetic resonance imaging was consistent with subacute combined degeneration in eight. Nerve conduction studies revealed a motor or sensorimotor axonal neuropathy (three with motor predominance). There was a bimodal demographic distribution consisting of socially isolated, international university students and local residents with a history of mental illness and polydrug abuse. Recreational N2 O use is an emerging health problem in Australia. International university students and patients with pre-existing mental illness or polydrug use appear to be at increased risk. A severe motor neuropathy may emerge following vitamin B12 replacement. Public health measures are required to limit the availability of N2 O and to educate adolescents and young adults about the potential for significant harm.

Analysis of clinical characteristics of subacute combined degeneration on three cases of delayed diagnosis

Purpose: Subacute Combined Degeneration (SCD) is a kind of neurodegenerative diseases which is easy to be misdiagnosed because of some promiscuous symptoms and atypical laboratory test results. The prognosis would be poor if patients had clinical symptoms of myelopathy for a long time. Therefore, doctors should combine pre-existing conditions, clinical symptoms and correlated laboratory examinations to make definite diagnosis quickly and accurately. Case report: Three middle-aged patients aged from 41 to 63, one male and two females were diagnosed SCD with progressive ascending numbness in four limbs or both legs. For some reason, none of them got the right diagnosis in the first place. In case 1, blood cell analysis revealed a decrease in three series including white blood cells, platelets and hemoglobin. In case 2, the blood cell analysis of the patient did not show signs of anemia at all. While the initial clinical symptom in case 3 was just a mild psychiatric symptom. Although their final diagnosis were clear, the failure not to take SCD into consideration at the first time was worthy of reflection. Fortunately, their neurological status improved after vitamin B12 supplementation. Conclusion: Usually, some confusing symptoms and a typical laboratory may make SCD easy to be misdiagnosed. Early diagnosis and treatment are critical to the prognosis. Thus, the clinicians must capture the related clinical characteristics. Keywords: subacute combined degeneration; vitamin b12 deficiency; clinical characteristics.

Analysis of clinical characteristics and prognostic factors in 110 patients with nitrous oxide abuse.

PurposeTo review the clinical symptoms, auxiliary examination findings, and outcomes of patients with nitrous oxide (N2O) abuse, and analyze the factors that affect outcomes.MethodsPatients with N2O abuse treated in the Department of Neurology between January 2018 and December 2020 were included. The clinical data of these patients were collected, and follow‐up was conducted to determine the outcomes.ResultsThe average age of the 110 patients with N2O abuse was 21.4 ± 4.2 years (range: 14–33 years). Clinical presentation primarily included neurological symptoms, such as limb numbness and/or weakness (97%), psychiatric symptoms, changes in appetite, and skin hyperpigmentation. Laboratory test results were characterized by vitamin B12 deficiency (60%, 34 out of 57 cases) and high homocysteine level (69%, 31 out of 45 cases). Electromyography indicated mixed axonal and demyelination injury (92%, 80 out of 87 cases). Motor and sensory nerves were simultaneously involved, and injury primarily involved the lower limbs. One hundred and seven (97%) patients were clinically diagnosed with peripheral neuropathy, of whom 26 (24%) exhibited spinal abnormalities on magnetic resonance imaging, supporting a diagnosis of subacute combined degeneration. Treatment included N2O withdrawal and vitamin B12 supplementation. Reexamination of six patients indicated that treatment was effective. Follow‐up was completed for 51 patients. Thirty‐four patients (67%) recovered completely, 17 patients (33%) had residual limb numbness, and only one patient experienced relapse. Sex was an independent prognostic factor; the outcomes of female patients were better than that of male patients.ConclusionThe recreational use of N2O has largely expanded among youth in recent decades, which has become a growing public health concern in China. It highlights the importance of the recognition of various clinical symptoms, particularly limb numbness and/or weakness related to the cases of N2O abuse. The therapeutic administration of vitamin B12 supplementation and N2O withdrawal can make the overall prognosis good, especially for female patients.

Clinical Presentation of Subacute Combined Degeneration in a Patient With Chronic B12 Deficiency.

Subacute combined degeneration (SCD) is a rare complication of chronic vitamin B12 deficiency that presents with a variety of neurologic findings, including decreased sensation in the extremities, increased falls, and visual changes. Treatment of SCD involves prompt replacement of vitamin B12 and addressing the underlying conditions that cause the deficiency. Given the prevalence of B12 deficiency in the older adult population, clinicians should remain alert to its possibility in patients who present with progressive neuropathy. This report presents a case of a patient with progressive SCD secondary to chronic B12 deficiency despite monthly intramuscular B12 injections. Appropriate B12 replacement is aggressive and involves intramuscular B12 1000 mcg every other day for 2 to 3 weeks, followed by additional IM administration every 2 months before transitioning to oral therapy. Failure to adequately replenish B12 can lead to progression or lack of resolution of SCD symptoms.

Early diagnosis and treatment of funicular myelosis in v12 deficiency anemia

Early diagnosis and treatment of funicular myelosis in v12 deficiency anemia

Co-Existence of Anterior and Posterior Column Lesions in Patients with Subacute Combined Degeneration

Subacute combined degeneration (SCD) of the spinal cord, which is a result of vitamin B12 deficiency, may cause irreversible neurological deficits. The lesion in the spinal cord is typically localized to the posterior and lateral columns, as the name implies. In this paper, we report on two patients with SCD, whose lesions involved the bilateral anterior column as well as the posterior and lateral columns. This report illustrates the importance of awareness of clinical and radiologic variable characteristics of SCD.

Subacute combined degeneration of spinal cord, optic atrophy and thrombocytopenia without anemia secondary to B12 deficiency

Long-standing vitamin B12 deficiency can lead to neurological manifestations such as optic atrophy and subacute combined degeneration of the cord without causing significant anemia. In addition, folic acid supplementation could mask the hematological manifestations of vitamin B12 deficiency and delay the presentation of neurological manifestations We present a case of a 32-year-old vegan woman on long-term sodium valproate and folic acid treatment presenting with progressive weakness of bilateral lower limbs for three months and reduced vision in both eyes for two weeks duration. Further evaluation revealed optic atrophy, combined degeneration of the spinal cord, macrocytosis, thrombocytopenia, and severely deficient serum B12 levels. With B12 replacement therapy, the patient’s overall wellbeing improved.

The association between serum total homocysteine and subacute combined degeneration of spinal cord

Objective: The research was aimed to investigate the association between serum total homocysteine (tHcy) and subacute combined degeneration of the spinal cord (SCD). Methods: A retrospective survey of 106 newly diagnosed patients with SCD were enrolled in this research who were treated in the department of neurology of Xijing Hospital from January 2008 to February 2019, meanwhile, 121 patients with spinal cord lesion (not SCD) and 104 neurology mild outpatients were selected as controls. Serum tHcy level was determined by using the chemiluminescent immunoassay assay. A multivariate logistic regression model was used to analyze the risk factors for SCD. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, sensitivity, specificity and Youden index were used to evaluate the diagnostic efficacy of tHcy. Spearman correlation analysis was used to observe the correlation between tHcy and SCD severity. The SCD patients were categorized into normal or mild tHcy group, moderate tHcy group, and severe tHcy group based on tHcy levels. Clinical symptoms, nerve conduction velocity, magnetic resonance imaging (MRI) findings from the patients were studied. Results: The serum tHcy levels in SCD patients were 64.3(26.5, 98.8) μmol/L, while in patients with spinal cord lesion (not SCD) group were 13.7(10.8, 19.2) μmol/L, neurology mild outpatients were 10.6(8.2, 13.0) μmol/L, which was higher in SCD group (H=112.020,P<0.001), (H=165.525,P<0.001).The multivariate logistic regression model showed tHcy is the impact factor of SCD (OR=1.107, 95%CI:1.077-1.139, P<0.001). At ROC analysis, tHcy showed diagnostic value with an optimal cut-off value of 24.9 μmol/L (AUC 0.913, 95%CI: 0.875-0.951, sensitivity 79.2%, specificity 91.6%). Spearman correlation analysis showed that tHcy was positively correlated with functional disability rating scale (r=0.254, P=0.009). Conclusions: Serum tHcy is the risk factor for SCD and related to its disability. Focus on the increased level of tHcy plays a positive role in the diagnosis of SCD.

The dangers of recreational inhalation of nitrous oxide.

Nitrous oxide, also known as 'laughing gas', is one of the most widely used recreational drugs among teenagers in the UK. Copious inhalation of nitrous oxide may increase intra-alveolar pressure, resulting in barotrauma secondary to alveolar rupture. Pneumomediastinum and subcutaneous emphysema are common clinical findings in nitrous oxide-associated barotrauma. Prolonged nitrous oxide misuse may inactivate vitamin B12 through the alteration of its metabolism, causing demyelination of the central and peripheral nervous system. A spectrum of neurological manifestations has been reported, including peripheral neuropathy, myelopathy and subacute combined degeneration of the spinal cord. Medical therapies and psychosocial interventions aiming at nitrous oxide cessation are important treatment steps to achieve partial or complete recovery from the adverse effects associated with inhalation of nitrous oxide.

Serum copper decrease and cerebellar atrophy in patients with nitrous oxide-induced subacute combined degeneration: two cases report

BackgroundSubacute combined degeneration (SCD) is a neurological complication commonly associated with vitamin B12 deficiency. It can result from nitrous oxide (N2O) abuse and cause neuropsychiatric symptoms. However, there has been no literature regarding alterations of serum copper and cerebellum in SCD patients.Case presentationWe reported two cases of young SCD patients with histories of N2O abuse. In these cases, elevated homocysteine, macrocytic anemia, spinal cord abnormalities, and peripheral nerve injuries were detected. In addition, decreased serum copper level and cerebellar atrophy were reported for the first time. The patients’ symptoms improved after withdrawal of N2O exposure and vitamin B12 supplements.ConclusionWe reported two SCD cases with serum copper alteration and cerebellar atrophy after N2O abuse for the first time. These might be crucial complements to the diagnosis of SCD.

Clinical epidemiological characteristics of nitrous oxide abusers: A single-center experience in a hospital in China.

PurposeThis study investigated the clinical epidemiological characteristics of nitrous oxide (N2O) abusers in a hospital in China, which have not been systematically reported.MethodsThe characteristics of patients abusing N2O who were examined and treated at the Affiliated Hospital of Xuzhou Medical University from January 2017 to December 2020 were analyzed.ResultsA total of 61 patients (average age: 21.7 ± 3.2 years; 42 male and 19 female) were enrolled; 60.7% of the patients had an education level of high school or lower, and most (59.0%) had no stable occupation. The mean exposure time was 8.5 ± 7.7 months (range: 1–36 months). Only 52.5% of the abusers reported the physician of the relevant exposure history at the first time of visiting the doctor. The main clinical type was mixed (49.2%). The most common clinical manifestation was distal limb numbness (80.3%). The most frequent outcome was peripheral neuropathy (59%) and subacute combined degeneration (36%). Serum homocysteine level was elevated in 67.5% (27/40) of the patients, while 44.4% (20/45) showed reduced vitamin B12. Note that 61% (22/36) showed abnormal signals in the posterior or lateral funiculus of the spinal cord, and 97% (31/32) of the patients showed peripheral nerve damage by electromyography. In all cases, symptoms were alleviated after halting N2O intake and receiving nutritional neurotherapy.ConclusionsN2O abuse can lead to nervous system damage, especially peripheral nerve and spinal cord damage. A full understanding of its clinical epidemiological characteristics is helpful for clinicians to make a timely and clear diagnosis.

Subacute Combined Degeneration Associated with Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism

Subacute combined degeneration (SCD) is a metabolic disease caused by deficiency of vitamin B12. Rarely, it could be associated with genetic problem. An old male presented with progressive both hands weakness. Laboratory study showed deficiency of vitamin B12, but the cause was not clear. We performed a genetic study and methylenetetrahydrofolate reductase (MTHFR) C677T homozygous polymorphism with 30% of normal enzyme activity was confirmed. This case suggests SCD may occur in association with a genetic problem with MTHFR C677T polymorphism.

Utility of magnetic resonance imaging in the evaluation of sensory ganglionopathy: A case series

Sensory ganglionopathy (SNN), is a disease of dorsal root ganglia and usually associated with paraneoplastic syndromes (anti-Hu associated), Sjögren syndrome, chemotherapeutic agents and paraproteinemia. Spinal MRI shows dorsal column involvement mimicking subacute combined degeneration of the cord. We present 3 cases of confirmed SNN with characteristic MRI findings.