Follow-up assessment of patients with Pure Neural Leprosy in a reference center in Rio de Janeiro—Brazil

Introduction Pure Neural Leprosy (PNL) is a rare clinical form of leprosy in which patients do not present with the classical skin lesions but have a high burden of the disability associated with the disease. Clinical characteristics and follow up of patients in PNL are still poorly described in the literature. Objective This paper aims to describe the clinical, electrophysiological and histopathological characteristics of PNL patients, as well as their evolution after multidrug therapy (MDT). Methods Fifty-two PNL patients were selected. Clinical, nerve conduction studies (NCS), histopathological and anti-PGL-1serology were evaluated. Patients were also assessed monthly during the MDT. At the end of the MDT, all of the patients had a new neurological examination and 44 were submitted to another NCS. Results Paresthesia was the complaint most frequently reported by patients, and in the neurological examination the most common pattern observed was impairment in sensory and motor examination and a mononeuropathy multiplex. Painful nerve enlargement, a classical symptom of leprosy neuropathy, was observed in a minority of patients and in the motor NCS axonal injuries, alone or in combination with demyelinating features, were the most commonly observed. 88% of the patients did not present any leprosy reaction during MDT. There was no statistically significant difference between the neurological examinations, nor the NCS pattern, performed before and after the MDT. Discussion The classical hallmarks of leprosy neuropathy are not always present in PNL making the diagnosis even more challenging. Nerve biopsy is an important tool for PNL diagnosis as it may guide therapeutic decisions. This paper highlights unique characteristics of PNL in the spectrum of leprosy in an attempt to facilitate the diagnosis and management of these patients.

CASE REPORT OF ADULT-ONSET CHARCOT MARIE TOOTH TYPE X

Charcot-Marie-Tooth (CMT) or Hereditary Motor and Sensory Neuropathy (HMSN) is the most common hereditary peripheral nerve disease with progressive chronic weakness, muscle atrophy, and sensory disturbances. There are several types and subtypes of CMT with their respective clinical manifestations. In this article, we reported a patient with of CMT type X. A 43-year-old male patient was referred to a neurology clinic with weakness in both limbs for 2 years, accompanied by tingling and sensory disturbance in both hands and feet. There are several of his family members who had similar complaints. Lumbosacral magnetic resonance imaging (MRI) examination revealed mild nucleus pulposus herniation. Electroneuromyography (ENMG) examination revealed demyelinating sensory motor polyneuropathy. Histopathological examination of nerve biopsy showed demyelination of the sural nerve. It is hard to make a diagnosis of CMT, because it requires high suspicion from clinicians once encounter a suspected case and also need to supported by sophisticated equipment such as electrophysiological examinations, nerve biopsy examinations, and genetic examinations. It is vital for clinicians for being able to diagnose CMT correctly and provide treatment as soon as possible in order to maintain the patients’ quality of life.

Guillain-Barre syndrome related to COVID-19: muscle and nerve biopsy findings

Background: The involvement of the peripheral nervous system (PNS) in COVID-19 is rare and, to date, morphological aspects from muscle and nerve biopsies have not been reported. Here, we describe a case of Guillain-Barré Syndrome (GBS) related to COVID-19 and demonstrate findings from peripheral nerve and skeletal muscle biopsies. A 79-year-old man presented with progressive weakness in both legs over one-week, evolving to both arms and urinary retention within 6 days. Four days earlier, he had a cough, febrile sensation and mild respiratory discomfort. On admission, his was afebrile, and without respiratory distress. A neurological examination disclosed asymmetric proximal weakness, diminished reflexes and no sensitive abnormalities. Three days later, the patient presented with bilateral facial weakness and proximal muscle strength worsened. Deep tendon reflexes and plantar responses were absent. Both superficial and profound sensitivity were decreased. From this point, oxygen saturation worsened, and the patient was placed on mechanical ventilation. CSF testing revealed one cell and protein 185 mg/dl. A chest CT showed the presence of ground-glass opacities and RT-PCR for SARS-CoV-2 was positive. The muscle biopsy revealed moderate neuromyopathic findings with positive expression for MHC-class I, C5b9, CD8 and CD68. The nerve biopsy showed inflammatory infiltrates predominantly with endoneurial compound formed by CD45 and CD68. The patient was treated with Oseltamivir for 9 days followed by IVIG for 5 days and died three days later of septic shock. Discussion: This is the first documented case of GBS associated with COVID-19 with a muscle and nerve anatomopathological study. A systematic review about neurological complications caused by COVID-19 described 11 patients with GBS. The morphological features reported in our patient showed signs of involvement of the immune system, suggesting that direct viral invasion could have played a role in the pathogenesis of peripheral nerve injury. Hereafter, further research will be necessary to understand the triggers for these cells migrating into the peripheral nerve.

Eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome) imitating Guillain–Barre syndrome (GBS): a case report

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is associated with vasculitic neuropathy and being rare can present as subacute symmetric sensorimotor quadriparesis mimicking Guillain–Barre syndrome (GBS). It warrants timely diagnosis as treatment for both conditions is different and vasculitic neuropathy needs long-term immunosuppression. Nerve biopsy of our patient showed eosinophilic infiltration along with mononuclear infiltrate. Typical histopathological presentations of EGPA are different among different organs and eosinophilic infiltration is rarely observed in peripheral nerve and kidney involvements. Case presentation A 49-year-old female with a history of asthma with 3-week duration of acute onset ascending weakness, preceded by severe pain and burning in glove and stocking pattern. Nerve conduction studies could not rule out Guillain–Barre syndrome initially, but subsequent studies show axonal affection and she received intravenous immunoglobulin (IVIg) but her weakness progressed after slight improvement. Her bloodwork revealed marked eosinophilia (> 50%) with computed tomography (CT) paranasal sinuses showing pansinusitis with background history of asthma led us towards eosinophilic granulomatosis with polyangiitis and later antineutrophil cytoplasmic antibodies came out positive with nerve biopsy showing perivascular mononuclear inflammation with eosinophils. She was started on steroids immediately and then received intravenous rituximab in view of long-term immunosuppression with maintenance steroids and on follow-up she improved. Conclusion Eosinophilic granulomatosis with polyangiitis is a small-vessel vasculitis associated with antineutrophil cytoplasmic antibodies with significant paranasal sinuses involvement. Mononeuritis multiplex is the most common presentation of vasculitic neuropathy of eosinophilic granulomatosis with polyangiitis, but they can mimic Guillain–Barre syndrome and should always be considered in the differential diagnosis, since the treatment strategies for these conditions are radically different.

The red flags of ulnar neuropathy in leprosy

The diagnosis of pure neural leprosy is more challenging because patients share characteristics with other common pathologies, such as ulnar compression, which should be taken into consideration for differential diagnosis. In this study, we identify ulnar nerve conduction characteristics to aid in the differential diagnosis of ulnar neuropathy (UN) in leprosy and that of non-leprosy etiology. In addition, we include putative markers to better understand the inflammatory process that may occur in the nerve. Data were extracted from a database of people affected by leprosy (leprosy group) diagnosed with UN at leprosy diagnosis. A non-leprosy group of patients diagnosed with mechanical neuropathy (compressive, traumatic) was also included. Both groups were submitted to clinical, neurological, neurophysiological and immunological studies. Nerve enlargement and sensory impairment were significantly higher in leprosy patients than in patients with compressive UN. Bilateral impairment was significantly higher in the leprosy group than in the non-leprosy group. Leprosy reactions were associated to focal demyelinating lesions at the elbow and to temporal dispersion (TD). Clinical signs such as sensory impairment, nerve enlargement and bilateral ulnar nerve injury associated with eletrodiagnostic criteria such as demyelinating finds, specifically temporal dispersion, could be tools to help us decided on the best conduct in patients with elbow ulnar neuropathy and specifically decide if we should perform a nerve biopsy for diagnosis of pure neural leprosy.

Vasculitic Tibial Mononeuropathy Associated with Inherited Immune Dysregulation: A Review of Tibial Mononeuropathies with Electrodiagnostic Considerations

Compressive tibial mononeuropathies are uncommon and can be caused by conditions including posterior compartment syndrome, soleal sling syndrome, and tarsal tunnel syndrome. Therefore, it is critical to consider noncompressive etiologies when a tibial mononeuropathy is suspected. This is a patient with a history of rare inherited immune dysregulation that presented to the electrodiagnostic laboratory with severe neuropathic pain in the right foot associated with plantarflexion weakness, concerning for a tibial mononeuropathy. However, the patient’s clinical presentation and results on electrodiagnostic testing were not consistent with any of the above entities. Therefore, noncompressive etiologies of tibial mononeuropathies such as vasculitis had to be considered. The patient subsequently underwent sural nerve biopsy which confirmed small-vessel vasculitis as the cause of the tibial mononeuropathy. She was then started on appropriate immunosuppressive treatment which resulted in significant pain relief and was discharged home. This case highlights the importance of considering noncompressive causes of tibial nerve injury. Compressive and vasculitic tibial mononeuropathies along with their electrodiagnostic considerations are reviewed. Furthermore, this case highlights the critical role of the electromyographer and ability to maximize the impact on patient care through a solid foundation in anatomy, pathophysiology, and electrodiagnosis blended with clinical acumen.

Difficult-to-Treat Polyradiculoneuropathy

A 51-year-old healthy man sought care for a 6-month history of progressive, distal, lower extremity weakness, imbalance, and numbness in the feet. Neurologic examination showed a steppage gait, upper and lower extremity weakness, distal greater than proximal, absent tendon reflexes, and large fiber–predominant sensation loss in the feet. Nerve conduction studies showed marked temporal dispersion and slowed conductions. Cerebrospinal fluid analysis showed an increased protein concentration, 1 white blood cell/µL, and normal glucose level. Lumbar spine magnetic resonance imaging showed enlargement and enhancement of the nerve roots in the cauda equina, along with hypointensity in lumbar vertebral bodies. He underwent right sural nerve biopsy that showed an inflammatory demyelinating process. The patient was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy and started on intravenous immunoglobulin. He was markedly worse at 12-week follow-up, with severe proximal and distal weakness and requiring the use of a walker. The diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy was revisited. Lumbar spine magnetic resonance imaging again showed enhancement of the nerve roots. Because of concern for neurolymphomatosis, a proximal fascicular nerve biopsy of the right sciatic nerve was performed. It showed the hallmark pathologic features of chronic inflammatory demyelinating polyradiculoneuropathy: endoneurial inflammation and signs of long-standing demyelination and remyelination with stacks on Schwann cell processes. The diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy was confirmed. Intravenous immunoglobulin was stopped, and the patient was started on an aggressive plasma exchange regimen. He had modest improvement. Azathioprine was also started. The patient continued to improve. He remained on this regimen for 2 years. Over the next year, the intravenous methylprednisolone dose was reduced. He was weaned off plasma exchange and intravenous methylprednisolone. At the last follow-up the disease was still in remission. Chronic inflammatory demyelinating polyradiculoneuropathy was described and named in 1975. It is a fairly symmetric peripheral neuropathy that usually presents with proximal and distal weakness, imbalance, and large fiber sensory dysfunction. Cerebrospinal fluid analysis shows albuminocytologic dissociation in 80% to 95% of those with typical chronic inflammatory demyelinating polyradiculoneuropathy.

Persistent Neuropathy in Lepromatous Leprosy Patients

Lepromatous leprosy (LL) patients have evidence of extensive peripheral nerve damage as soon as a diagnosis is made, but most of them have few or no symptoms related to peripheral neuropathy. Usually, they do not have the cardinal signal of leprosy neuritis. However, disability caused by peripheral nerve injuries has consequences throughout the entire life of these patients and the pathophysiological mechanisms of nerve damage are still poorly understood. The objective of this study was to evaluate the outcome of peripheral neuropathy in a group of LL patients in an attempt to understand the mechanisms of nerve damage. We evaluated medical records of 14 LL patients that had undergone a neurological evaluation at the beginning of Leprosy treatment then worsened at least 4 years after the end of treatment and underwent nerve biopsy. The symptoms at the beginning of treatment were compared with those at the time of the biopsy. Pain was a symptom in only one patient at the beginning and was a complaint in 9 patients by the time of biopsy. Neurological examination showed that the majority of patients already had alterations in medium and large caliber fibers at the beginning of the treatment, and pain increased by the time of biopsy, while neurological symptoms and signs deteriorated independently of the use of prednisone or thalidomide. Nerve Conduction Studies demonstrated that sensory nerves were the most affected. LL patients can develop a silent progressive degenerative peripheral neuropathy, which continues to develop despite high dose long term corticoid therapy.

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.