In addition to polyneuropathy, patients with hereditary transthyretin amyloidosis (ATTRv) often experience autonomic dysfunction, which reduces quality of life. Compared with patients with ATTRv from endemic areas, those from non-endemic areas rarely develop autonomic dysfunction as an initial symptom. Conversely, autonomic dysfunction can be a diagnostic red flag in patients from non-endemic areas without a family history. Autonomic dysfunction in patients with wild-type transthyretin amyloidosis (ATTRwt) has only recently been reported. However, further knowledge is needed to clarify its pathophysiology.

Guillain-Barré syndrome is an acute-onset, immune-mediated neuropathy characterized by humoral immune attacks on peripheral motor and sensory nerve fibers, with predominant motor involvement. Autonomic dysfunction, typically characterized by sympathetic hyperactivity, is common and varies in severity, occasionally affecting prognosis. This autonomic dysfunction is considered to result from conduction failure in autonomic nerve fibers, similar to the damage observed in motor and sensory fibers. It remains unclear whether this process results from an immune response against common antigens expressed on motor, sensory, and autonomic nerves or from an immune reaction against antigens specific to the autonomic nervous system that occurs concurrently with attacks on motor and sensory nerves. This paper summarizes the clinical semiology and pathological and physiological findings of autonomic dysfunction in Guillain-Barré syndrome and discusses its pathophysiology by comparing it with other immune-mediated autonomic neuropathies.

To identify potential red flag diagnoses in a cohort of patients seeking care for LBP, compare prevalence rates based on the setting of initial diagnosis, and identify demographic risk factors. A longitudinal cohort study using US Military Health System Data Repository data, identifying all patients seeking care for LBP in military clinics between January 2015 and December 2019. LBP cases and red-flag conditions were identified using diagnostic codes in electronic medical records. The setting of initial LBP diagnosis was also identified (immediate care: emergency/urgent care clinics, versus all others). 1,214,604 individuals sought care for LBP and met study criteria (37.7% female, 55.3% active duty, mean age: 34.7 years), with 10.2% initially seen in immediate care settings. A total of 2.9% of patients received a red-flag diagnosis within 90 days of the index LBP visit, ranging from 0.02% for cauda equina syndrome, vertebral fracture, abdominal aortic aneurysm, and ankylosing spondylitis to 1.2% for infection. Immediate care as the setting of initial LBP diagnosis, female sex, non-active-duty, and increasing age increased the odds for most red flag diagnoses. In patients seeking care for LBP, serious pathology was uncommon; only 2.9% with red flag diagnoses (3.2% immediate care versus 2.2% other settings). The rate of red flag diagnoses was significantly higher among patients initially seen in immediate care, except for cancer, gynecological disorders, and ankylosing spondylitis. Active-duty service members had higher odds for vertebral fractures and cancer, while males had higher risk for abdominal aortic aneurysm.

Hereditary sensory and autonomic neuropathy type IV (HSAN IV), also known as congenital insensitivity to pain with anhidrosis (CIPA), is a very rare autosomal recessive neurological disorder caused by pathogenic variants in the NTRK1 gene. It is clinically characterized by insensitivity to pain, anhidrosis with recurrent febrile episodes, orthopedic complications secondary to repeated trauma, and, in some cases, intellectual disability. We report the case of a 43-year-old female patient with insensitivity to pain since the neonatal period, mild developmental delay, lingual self-mutilation, recurrent fever without infectious focus, Charcot-like joint deformities, and severe orthostatic hypotension. Neurological examination revealed generalized hypoalgesia and distal weakness in the lower limbs, corroborated by electrophysiological studies. Lumbar spine magnetic resonance demonstrated severe structural involvement, and Ewing's test documented both sympathetic and parasympathetic autonomic dysfunction. Genetic analysis identified the pathogenic NTRK1 variant (NM_002529.4): c.2311C>T; p.(Arg771Cys) in homozygosity, previously reported in individuals with CIPA. This finding was confirmed by intrafamilial segregation analysis, which demonstrated the homozygous status of the patient and heterozygous carrier status in her siblings. We present this case because of its rarity, its molecular confirmation, and its remarkable clinical manifestations, highlighting the importance of genetic diagnosis in rare neurological diseases.

Immunoglobulin light chain (AL) amyloidosis and POEMS syndrome are plasma cell proliferative disorders involving multiple organs and tissues, often presenting with nonspecific clinical manifestations. The co-occurrence of both conditions in a single patient is clinically rare and can easily lead to misdiagnosis or underdiagnosis. This report describes an elderly male patient who presented primarily with refractory heart failure and was ultimately diagnosed with coexisting AL amyloidosis and POEMS syndrome. The patient received 12 cycles of treatment with bortezomib, cyclophosphamide, and dexamethasone (BCD), achieving significant clinical and biochemical remission. This case underscores that while the coexistence of rare diseases is uncommon, it represents an important cause of clinical complexity and treatment resistance. A comprehensive etiological diagnosis is therefore a crucial prerequisite for formulating an effective and individualized treatment plan.

Epidemiology and treatment of HIV changed substantially within the last three decades. However, HIV-associated neurological disorders such as mild forms of HIV-associated neurocognitive disorder (HAND) as well as HIV-associated distal symmetrical sensory polyneuropathy are amongst the most frequent complications in patients with longstanding HIV infection. Opportunistic infections occur less frequently compared to former years, but especially in patients with late presentation of HIV progressive multifocal leukoencephalopathy (PML) (0.7 per 1,000 patient-years), toxoplasma encephalitis (0.4 per 1,000 patient-years) and cryptococcal meningitis (0.2 per 1,000 patient-years) remain the most common opportunistic infections. The guidelines for diagnosis and treatment of HIV-associated neurological disorders of the German Society of Neurology were revised addressing recent changes in treatment opportunities of HAND, HIV associated complications of the peripheral nervous system and muscles and opportunistic infections of the central nervous system (CNS).

Hereditary transthyretin (ATTRv) amyloidosis is a rare, progressive multisystem disease caused by pathogenic variants in the transthyretin (TTR) gene. ATTRv-associated Polyneuropathy (ATTRv-PN) manifests in a length-dependent sensorimotor and autonomic pattern, commonly accompanied by cardiomyopathy. In recent years, clinical trials have introduced two classes of disease modifying treatments (DMT), TTR stabilizers and gene silencers. Across populations and outcome parameters, all trials share one result disease progression was significantly slowed and patients' span and quality of life substantially improved compared to placebo, even though a function once lost would not be retrieved. This expert consensus paper provides recommendations for the treatment of ATTRv-PN in Germany and was jointly developed by experts from the German Society of Amyloid Diseases (DGAK) and the German Neurological Society (DGN). In addition to evidence from pivotal clinical trials, the recommendations incorporate benefit assessments of the German Federal Joint Committee (G-BA). For first-line treatment, the DGAK/DGN recommends one of the two second-generation TTR gene-silencing agents, vutrisiran or eplontersen, for most patients with symptomatic ATTRv-PN. For patients showing even minor signs of disease progression under a TTR stabilizer, the authors recommend immediate switch to a gene silencer. Evidence is limited for or against switching between silencers or combining different agents. Informed patient participation is crucial upon initiation and adaptation of DMT. For central nervous system (CNS) involvement, none of the approved agents sufficiently crosses the blood-brain barrier. Aligned with that, there are no observed or expected CNS side effects of any of the DMTs. In the future, next-generation RNA-interference therapies, gene-editing approaches, and amyloid-depleting antibodies are expected to further expand therapeutic options.

The basic characteristic of chronic idiopathic demyelinating polyneuropathy (CIDP) is demyelination of peripheral nerves of autoimmune origin. Antibodies against various myelin sheath proteins play an important role in the pathogenesis of the disease. Cell-mediated immunity, characterised by T-cell and macrophage infiltration in peripheral nerves and spinal roots, is also significantly involved (1). Treatment of CIDP is aimed at suppressing inflammation, but also at removing autoantibodies, cytokines and other pro-inflammatory molecules from the blood. Treatment options include corticosteroids, (intravenous or subcutaneous) immunoglobulins, and plasma exchange (plasmapheresis). If a patient with CIDP does not show an adequate clinical response to these three treatment modalities, it is then refractory CIDP. Based on various studies, this affects up to 10% of patients. We present here a patient with CIDP whose condition gradually stopped improving after all three commonly used treatment modalities (corticosteroids, immunoglobulins, and plasmapheresis). His neurological findings were very severe. The case was ultimately diagnosed as a refractory form of CIDP, which is discussed here in the light of current knowledge of this issue.

A 63-year-old man with extensive multilevel degenerative cervical and thoracic spine disease, class 1 obesity, essential hypertension, mixed hyperlipidemia, and a history of type 2 diabetes mellitus presented with progressive bilateral upper and lower extremity paresthesias, burning pain in the hands and feet, gait instability, and a history of a fall with transient loss of consciousness. Initial workup revealed a hemoglobin A1c (HbA1c) of 5.4%, and an extensive neuropathy panel was unrevealing. Imaging demonstrated ossification of the posterior longitudinal ligament (OPLL) with multilevel central canal stenosis and cord deformity without cord signal change. The clinical picture was attributed primarily to cervical myelopathy, and the patient underwent anterior cervical discectomy and fusion (ACDF) at C3-C4 and C6-C7. Postoperatively, symptoms failed to improve and progressively worsened, with new-onset dense numbness involving the face and oral mucosa. Serial HbA1c measurements revealed a dramatic rise from 5.4% at initial presentation to 5.9% two months later and ultimately to 13.8% approximately seven months after initial presentation, unmasking poorly controlled type 2 diabetes as a likely major contributor to the patient's length-dependent sensorimotor polyneuropathy. This case underscores that diabetic peripheral neuropathy (DPN) can present and progress even when HbA1c is within the non-diabetic range, particularly in patients with metabolic syndrome, and that structural spinal pathology may coexist with, but not fully explain, progressive neurological symptoms.