The efficacy of immunotherapies such as steroids, plasmapheresis, and intravenous immunoglobulin have been proven in various immune-mediated neuropathies. However, these treatments sometimes lack the efficacy in a part of patients with the immune-mediated neuropathies. In addition, anti-myelin associated glycoprotein (MAG) neuropathy is usually refractory to the treatments. Recently, novel therapies targeting a molecule which are associated with pathogenesis of immune-mediated diseases, have been developed. These molecularly targeted therapies are notable in immune-mediated neuropathies as novel drug candidates. In the present article, current treatments and future prospect of novel therapies in immune-mediated neuropathies will be reviewed.

Heme is an iron-containing molecule essential for virtually all living organisms. However, excessive heme is cytotoxic, necessitating tight regulation of intracellular heme concentration. The acute hepatic porphyrias (AHPs) are a group of rare inborn errors of heme biosynthesis that are characterized by episodic acute neurovisceral attacks that are precipitated by various factors. The AHPs are often misdiagnosed, as the acute attack symptom are non-specific and can be attributed to other more common causes. Understanding how heme biosynthesis is dysregulated in AHP patients and the mechanism by which acute attacks are precipitated will aid in accurate and rapid diagnoses, and subsequently, appropriate treatment of these disorders. Therefore, this review article will focus on the biochemical and molecular changes that occur during an acute attack and present what is currently known regarding the underlying pathogenesis of acute attacks.

A 70-year-old male who has medical history of Parkinson’s disease for 26 years admitted to our hospital for trial of levodopa carbidopa intestinal gel (LCIG) therapy because of severe dyskinesia and frequent wearing-off. He developed deterioration when he was treated with one of the levodopa (LD) decacrboxylase inhibitor compounds in the past. Five days after LD had changed into equivalent dose of LD/carbidopa (CD), high fever with hyperCKemia appeared. He was diagnosed as having Parkinsonism-hyperpyrexia syndrome (PHS). Exchange of LD/CD to LD drugs improved the symptoms quickly. Four days after LCIG administration, PHS reappeared. Simultaneously, the patient developed sepsis and disseminated intravascular coagulation (DIC). Thrombocytopenia did not improve after recovery from infection and DIC. Anti-PA IgG and drug-induced lymphocyte stimulation test (DLST) against LCIG showed positive. Exchange of LCIG to LD drugs and intravenous methylprednisolone administration improved the symptoms and thrombocytopenia. CD induced type II and type IV allergy were suspected. This case offers a caution that physicians should be aware of drug allergy in cases of which unexpected symptoms occurred in altering one LD compound to another.

The first case was a 75-year-old woman with intermittent sensory impairment of the left hand. FLAIR of the head MRI revealed hyperintensity along the pia mater in the right parieto-temporal lobe with few microbleeds. Our second case was a 78-year-old man who presented with motor aphasia. His MRI showed swollen cortex on FLAIR and cortical hemosiderosis on T₂* weighted imaging of the right cerebral hemisphere. Pathological findings indicated the first case as cerebral amyloid angiopathy (CAA)-related inflammation and the second case as CAA. Additionally, after brain biopsy, widespread white matter lesions were detected in the area surrounding the biopsy site. However, both patients showed improvement without immunotherapy. Therefore, it is important to consider whether immunotherapy is required when white matter lesions appear in the area surrounding the biopsy site.

A 36-year-old man has developed weakness of left thumb and atrophy of left thenar muscle and left first dorsal interosseous muscle without sensory disturbance for a year. A nerve conduction study revealed decreases in the amplitude of compound muscle action potentials and occurrence of F-waves on left medial nerve. Needle electromyography examination revealed positive sharp waves and later recruited motor units on left abductor pollicis brevis muscle. Brain MRI showed atrophy of bilateral cerebellar hemisphere. His grandmother and his two uncles have been diagnosed as spinocerebellar degeneration. After discharge, he developed bilateral lower limb ataxia. Genetic analysis showed heterozygous CAG repeat expansion (19/39) in ATXN2 gene, being diagnosed as spinocerebellar ataxia 2 (SCA2). A previous report has shown that motor neuron involvement is recognized as part of SCA2 in the same pedigree with full CAG repeat expansions in ATXN2 gene. We here report the patient with lower motor neuron involvement as an initial symptom of SCA2.

A 33-year-old female was admitted to our department complaining of multifocal paresthesia and weakness of the upper and lower extremities that had developed over the previous three months. She had also been undergoing treatment for atopic dermatitis with dupilumab, an anti-interleukin 4/13 receptor antibody. A nerve conduction study revealed multifocal axonal sensorimotor neuropathy of bilateral limbs. On admission, a small erythema appeared on her right forearm, but it was atypical for vasculitic skin lesions due to its location and time course. Nonetheless, a biopsy revealed medium-sized vessel vasculitis. The patient was therefore diagnosed with vasculitic neuropathy caused by cutaneous arteritis. Methylprednisolone pulse therapy with prednisolone and azathioprine markedly improved her symptoms. A skin biopsy is useful when mononeuropathy multiplex is suspected, even if the skin findings are atypical for vasculitic rash.

Diagnosing neuralgic amyotrophy can be challenging in clinical practice. Here, we report the case of a 37-years old Japanese woman who suddenly developed neuropathic pain in the right upper limb after influenza vaccination. The pain, especially at night, was severe and unrelenting, which disturbed her sleep. However, X-ray and MRI did not reveal any fractures or muscle injuries, and brain MRI did not reveal any abnormalities. During neurological consultation, she was in a posture of flexion at the elbow and adduction at the shoulder. Manual muscle testing suggested weakness of the flexor pollicis longus, pronator quadratus, flexor carpi radialis (FCR), and pronator teres (PT), while the flexor digitorum profundus was intact. Medical history and neurological examination suggested neuralgic amyotrophy, particularly anterior interosseous nerve syndrome (AINS) with PT/FCR involvement. Innervation patterns on muscle MRI were compatible with the clinical findings. Conservative treatment with pain medication and oral corticosteroids relieved the pain to minimum discomfort, whereas weakness remained for approximately 3 months. For surgical exploration, lesions above the elbow and fascicles of the median nerve before branching to the PT/FCR were indicated on neurological examinations; thus, we performed high-resolution imaging to detect possible pathognomonic fascicular constrictions. While fascicular constrictions were not evident on ultrasonography, MR neurography indicated fascicular constriction proximal to the elbow joint line, of which the medial topographical regions of the median nerve were abnormally enlarged and showed marked hyperintensity on short-tau inversion recovery. In patients with AINS, when spontaneous regeneration cannot be expected, timely surgical exploration should be considered for a good outcome. In our case, MR neurography was a useful modality for assessing fascicular constrictions when the imaging protocols were appropriately optimized based on clinical assessment.