A severe case of neuroleukemiosis caused by B cell chronic lymphocytic leukemia, presenting as mononeuritis multiplex.

To report an exceptional case of nerve infiltration by an otherwise benign chronic B cell leukemia, inducing severe mononeuritis multiplex. The patient underwent extensive evaluation, including nerve conduction study and myography, brain and plexus MRI, and nerve biopsy. The clinical and electrophysiological diagnosis was a mononeuritis multiplex with severe motor and sensory involvement; only the nerve biopsy allowed definite diagnosis and introduction of chemotherapy, leading to resolution of sensory deficit and progressive motor improvement. Neuroleukemiosis caused by chronic lymphoid leukemia is an exceptional diagnosis. The presence of other possible causes like cryoglobulinemia could induce avoidance of nerve biopsy thus undertreating patient, since steroid treatment is not expected to be efficient on lymphocytic proliferation. Our case stretches the importance of nerve biopsy and raises neuromuscular specialist's awareness of this rare entity

Prospective study on usefulness of sural-nerve biopsy

Background: Peripheral neuropathies are a heterogeneous group of disorders, but common among patients attending neurology clinics. A systematic approach, like sural nerve biopsy, is the need of the hour, for a cost effective diagnosis. Studies have shown that nerve biopsy improves treatment in up-to 60% patients. Present study was conducted to evaluate the clinical profile and usefulness of sural nerve biopsy in peripheral neuropathy.Methods: A prospective study was conducted in the Department of Neurology in collaboration with Department of Pathology, Medanta: The Medicity, Gurugram, for a period of six months from January 2019- June 2019. Out of total 82 randomly selected patients, 43 patients were selected for nerve biopsy.Results: Mean age in the biopsy group was 45.61±19.24 years. Duration of illness was less than 1 year in 60.5% patients. In 39.5% of cases, nerve biopsies established the diagnosis and in total 77% of cases it was worthwhile.  Hansen’s disease was diagnosed in 44%, CIDP in 12%, Vasculitis in 14%, and diabetes in 7% patients. Biopsy proved more diagnostic when tingling and numbness was there. Diminished DTRs was also statistically significant symptom in biopsy favoring group. Nerve biopsy in multiple mononeuropathy (65.1%) proved more beneficial than in polyneuropathy (32.6%). Similarly, motor-sensory was a predominant presentation in 28 (65.1%) patients with nerve biopsy being more valuable.Conclusions: Nerve biopsy, having a good diagnostic yield, can be a useful aid in cases with multiple mono-neuropathy. It can be the key to prevent long term neurological complications in patients.

Mechanisms of nerve damage in neuropathies associated with hematological diseases: lesson from nerve biopsies

Despite the introduction of non-invasive techniques in the study of peripheral neuropathies, sural nerve biopsy remains the gold standard for the diagnosis of several neuropathies, including vasculitic neuropathy and neurolymphomatosis. Besides its diagnostic role, sural nerve biopsy has helped to shed light on the pathogenic mechanisms of different neuropathies. In the present review, we discuss how pathological findings helped understand the mechanisms of polyneuropathies complicating hematological diseases

A study on diagnostic significance of nerve conduction studies in early detection of Pure Neuritic Hansen’s disease

INTRODUCTION: Hansen's disease is diagnosed by presence of skin lesions. However, in case of pure neuritic hansen's the diagnosis is delayed because of absence of skin lesions. The delay in diagnosis leads to delay in treatment which leads to formation of deformities. This study is aim that whether nerve conduction studies are helpful in subjecting the patient to early nerve biopsy. AIM OF THE STUDY: To study the diagnostic significance of nerve conduction studies in early detection of pure neuritic hansen's disease. MATERIALS AND METHODS: This study is a descriptive study of analysing the patients with clinical suspicion of pure neuritic Hansen's electro physiologically and later corrlating with the nerve biopsy results. 70 patients attending neurology OPD with clinical suspicion of pure neuritic hansen's disease were selected. Patients were evaluated for other diseases which can mimic Hansen's disease. Patients were subjected to sural nerve biopsy and then the findings were correlated with electro physiology. RESULTS: 16 out of 70 patients were diagnosed to have Hansen's disease by biopsy. The most common mimickers for Hansen's were Diabetic Neuropathy, HMSN and connective tissue disorders. Nerve conduction studies including sympathetic skin response were abnormal in all patients with Hansen's disease. It was also abnormal in other diseases like Diabetic Neuropathy and connective tissue disorders. CONCLUSION: All the patients with biopsy proven Hansen's disease showed abnormal nerve conduction studies. Since nerve conduction studies were also abnormal in other diseases it is not specific for Hansen's and based on that alone we cannot subject the patients for nerve biopsy. Nerve biopsy clinches the diagnosis

A review on the investigation of peripheral neuropathy at Mater Dei Hospital

The term peripheral neuropathy encompasses a wide range of disorders. The underlying causes of peripheral neuropathy are diverse. It is very difficult to ascertain the incidence of peripheral neuropathy with any degree of certainty, but it is a manifestation of several common multisystem disorders, whose incidence is on the rise, such as diabetes and Human Immunodeficiency (HIV) virus infection. Worldwide, the population prevalence is about 2,400 per 100,000 (2.4%), rising with age to 8,000 per 100,000 (8%).1 Peripheral neuropathy can significantly impact an individual's quality of life especially if undiagnosed and untreated. Investigation of peripheral neuropathy is expensive and time consuming, and is best performed in a stepwise approach. Even in the best of circumstances, an aetiological diagnosis is not always achieved. At present, the existing guidelines deal with the treatment of peripheral neuropathy but there are none on how patients with peripheral neuropathy should be investigated.peer-reviewe

Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study

BACKGROUND: Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset between age 10 and 22 years, cerebellar atrophy, peripheral neuropathy, oculomotor apraxia (OMA), and elevated serum alpha-fetoprotein (AFP) levels. Recessive mutations in SETX have been described in AOA2 patients. OBJECTIVE: To describe the clinical features of AOA2 and to identify the SETX mutations in 10 patients from four Italian families. METHODS: The patients underwent clinical examination, routine laboratory tests, nerve conduction studies, sural nerve biopsy, and brain MRI. All were screened for SETX mutations. RESULTS: All the patients had cerebellar features, including limb and truncal ataxia, and slurred speech. OMA was observed in two patients, extrapyramidal symptoms in two, and mental impairment in three. High serum AFP levels, motor and sensory axonal neuropathy, and marked cerebellar atrophy on MRI were detected in all the patients who underwent these examinations. Sural nerve biopsy revealed a severe depletion of large myelinated fibers in one patient, and both large and small myelinated fibers in another. Postmortem findings are also reported in one of the patients. Four different homozygous SETX mutations were found (a large-scale deletion, a missense change, a single-base deletion, and a splice-site mutation). CONCLUSIONS: The clinical phenotype of oculomotor apraxia type 2 is fairly homogeneous, showing only subtle intrafamilial variability. OMA is an inconstant finding. The identification of new mutations expands the array of SETX variants, and the finding of a missense change outside the helicase domain suggests the existence of at least one more functional region in the N-terminus of senataxin

Marked efficacy of Rituximab in multifocal motor neuropathy associated with chronic lymphocytic leukemia

The authors describe a patient who presented a multifocal motor neuropathy (MMN) associated with a high anti-ganglioside antibody (anti-GM1 and anti-GD1) titer at the clinical onset of a B-cell chronic lymphocytic leukemia (B-CLL). Immunomodulation (IVIg plus cyclosporine) resulted in a neurological improvement and reduced anti-ganglioside antibody titers, both of which remained stable for at least six years. After this period, the patient had a severe relapse of the neuropathy, which was independent of the clinical course of the B-CLL. Both IVIg and cyclophosphamide were ineffective, and the patient became tetraplegic within six months; in the meantime, the patient displayed an increased antiganglioside antibody titer. Treatment with rituximab (RTX), which is designed to selectively inhibit B cell function, resulted in a dramatic, prompt and long-lasting neurological improvement as well as a reduced anti-ganglioside antibody titer. Although there are no previous reports of MMN in patients with B-CLL, the efficacy of RTX in the treatment of MMN in this patient may be considered remarkable. The expansion of B-cell clones may be a prerequisite for RTX effectiveness in MMN, and in dysimmune neuropathies in general

Marked efficacy of rituximab in multifocal motor neuropathy associated with chronic lymphocytic leukemia

The authors describe a patient who presented a multifocal motor neuropathy (MMN) associated with a high anti-ganglioside antibody (anti-GM1 and anti-GD1) titer at the clinical onset of a B-cell chronic lymphocytic leukemia (B-CLL). Immunomodulation (IVIg plus cyclosporine) resulted in a neurological improvement and reduced anti-ganglioside antibody titers, both of which remained stable for at least six years. After this period, the patient had a severe relapse of the neuropathy, which was independent of the clinical course of the B-CLL. Both IVIg and cyclophosphamide were ineffective, and the patient became tetraplegic within six months; in the meantime, the patient displayed an increased antiganglioside antibody titer. Treatment with rituximab (RTX), which is designed to selectively inhibit B cell function, resulted in a dramatic, prompt and long-lasting neurological improvement as well as a reduced antiganglioside antibody titer. Although there are no previous reports of MMN in patients with B-CLL, the eficacy of RTX in the treatment of MMN in this patient may be considered remarkable. The expansion of B-cell clones may be a prerequisite for RTX effectiveness in MMN, and in dysimmune neuropathies in general

Advances in the diagnosis, immunopathogenesis and therapies of IgM-anti-MAG antibody-mediated neuropathies.

Polyneuropathy with immunoglobulin M (IgM) monoclonal gammopathy is the most common paraproteinemic neuropathy, comprising a clinicopathologically and immunologically distinct entity. The clinical spectrum spans from distal paresthesias and mild gait imbalance to more severe sensory ataxia, with falls and a varying degree of distal sensorimotor deficits. In approximately 75% of patients, the monoclonal IgM immunoreacts with myelin-associated glycoprotein (MAG) and sulfoglucuronyl glycosphingolipid (SGPG), or other peripheral nerve glycolipids that serve as antigens. These antibodies are considered pathogenic because IgM and complement are deposited on the myelin sheath, splitting the myelin lamellae, while adoptive transfer of patients\u27 IgM into susceptible host animals causes sensory ataxia and reproduces the human pathology. In spite of the apparently convincing pathogenicity of these antibodies, the response to immunotherapies remains suboptimal. Clorambuscil, cladibrine, cyclophospamide and intravenous immunoglobulin may help some patients but the benefits are minimal and transient. Open-label studies in \u3e200 patients indicate that rituximab is helpful in 30-50% of these patients, even with long-term benefits, probably by suppressing IgM anti-MAG antibodies or inducing immunoregulatory T cells. Two controlled studies with rituximab did not however meet the primary endpoint, mostly because of the poor sensitivity of the scales used; they did however show statistical improvement in secondary endpoints and improved clinical functions in several patients. This review provides an overview of the clinical phenotypes and immunoreactivity of IgM to glycolipids or glycoproteins of peripheral nerve myelin, summarizes the progress on treatment with rituximab as a promising therapy, discusses the pitfalls of scales used, identifies possible biomarkers of response to therapy and highlights the promising new anti-B cell or target-specific immunotherapies

The use of nerve and muscle biopsy in the diagnosis of vasculitis: a 5 year retrospective study

INTRODUCTION: Peripheral nerve vasculitis is an important condition which can be diagnostically challenging and is one of the principal current indications for nerve and muscle biopsy. Previous studies have suggested that combined nerve and muscle biopsy (usually of the superficial peroneal nerve and peroneus brevis muscle) produces a higher diagnostic yield than nerve biopsy alone in the investigation of vasculitis. OBJECTIVE: To determine whether in our two centres combined nerve (usually the sural) and muscle (usually the vastus lateralis) biopsy improved diagnostic yield compared with nerve biopsy alone. METHODS: We interrogated our database of all nerve biopsies (usually of the sural nerve) performed at our institutions over 5 years and identified 53 cases of biopsy proven peripheral nerve vasculitis. Clinicopathological and neurophysiological data in these patients were reviewed. RESULTS: The most common clinical presentation was with a painful asymmetric axonal polyneuropathy or mononeuritis multiplex (66% of cases). Nerve biopsy demonstrated definite vasculitis in 36%, probable vasculitis in 62% and no vasculitis in 2% of cases. In 24 patients a muscle biopsy (usually the vastus lateralis) was also performed and vasculitis was demonstrated in 46% of these (in 13% showing definite and 33% probable vasculitis). There was only one patient in whom vasculitis was demonstrated in muscle but not in peripheral nerve. CONCLUSION: Combined nerve (usually sural) and vastus lateralis muscle biopsy did not significantly increase the diagnostic yield compared with nerve biopsy alone. A sensible approach to the diagnosis of peripheral nerve vasculitis is to choose a nerve to biopsy which is clinically affected and amenable to biopsy. If the sural nerve is chosen, the data suggest that it is not routinely worth doing a vastus lateralis biopsy at the same time, whereas if the superficial peroneal nerve is chosen, it seems appropriate to do a combined superficial peroneal nerve and peroneus brevis biopsy. It is still not known if both the sural and superficial peroneal nerves are involved clinically which one gives the higher yield if biopsied