Small fiber neuropathy (SFN) is a relatively common, but largely understudied neurological syndrome which has affected the lives of many globally. The common symptoms of SFN include pain, dysesthesia, and autonomic dysfunction, which are caused by damage to small nerve fibers. Due to its heterogeneous nature, SFN causes a multitude of symptoms which makes the disease and its subtypes difficult to diagnose. Furthermore, as the pathophysiology of SFN remains largely enigmatic, no cause is found in around 50% of the cases and these are classified as idiopathic SFN (iSFN). The difficult task of diagnosing SFN, and the even more elusive feat of hunting for the underlying etiology, demands accurate, precise, preferably noninvasive, and affordable tools, or a combination of them. Accordingly, appropriate biomarkers for SFN are needed to stratify patients and develop cause-centered treatments in addition to symptomatic treatments. As peripheral axons grow and repair, identifying underlying causes of SFN and intervening early may spur axonal regeneration in young patients, which can greatly improve their symptoms and improve quality of life. This narrative review aims to objectively highlight functional, histological, and molecular biomarkers to aid clinicians in discerning the diagnostic tests they should use to diagnose, confirm and determine the etiology of SFN. The strengths and limitations of each potential biomarker will be discussed. Clearer diagnostic criteria, guidelines, and work-up for SFN are required for clinicians to better identify the disease in patients presenting with non-specific symptoms.

Catatonia is a neuropsychiatric syndrome characterized by a broad range of motor, behavioral and cognitive abnormalities. Catatonia and Parkinson’s disease (PD) may show partially overlapping symptomatology. For this reason, catatonia could be misdiagnosed and overlooked in patients with severe PD, leading to a delay in proper treatment with benzodiazepines or electroconvulsive therapy (ECT). Two cases of women with PD and catatonia who have been admitted and treated with ECT at the University Hospital of Pisa are described here. Both had a history of bipolar disorder and developed withdrawn catatonia, in the context of affective episodes, approximately one year after the diagnosis of PD. In both cases, ECT was needed and successfully led to the remission of catatonic symptoms, without cognitive worsening. Since ECT appears to effectively treat catatonia in patients with PD, clinicians should consider it as a therapeutic option.

The patient was a 6-year-old child with spastic quadriplegic cerebral palsy (CP) categorized with the gross motor function classification system (GMFCS) as a level IV and a Modified Modified Ashworth Scale (MMAS) of 2 for the bilateral hamstring and hip adductor muscles, and 3 for the bilateral gastrocnemius muscles. This patient’s limited range of motion significantly affected the caregiver’s ability to perform activities of daily living (ADLs). Dry needling (DN) is considered a standard treatment (TX) when treating adults with poor range of motion. This article aims to place intramuscular electrical stimulation (IMES), the delivery of an electrical current through a monofilament needle into targeted trigger points (TrPs) within the context of treating children with spastic CP. Following IMES TXs over 32 months that totaled 12 left hamstring TXs, 13 right hamstring TXs, 13 hip adductor TXs, 21 left gastrocnemius TXs, and 18 right gastrocnemius TXs, the patient demonstrated an increase in passive range of motion (PROM) of the hamstring, hip adductors, and gastrocnemius muscles. These gains equated to ease in ADLs. Both the Pediatric Evaluation of Disability Inventory (PEDI, PEDI-Caregiver Assistance Scale) and the Goal Attainment Scale (GAS) demonstrated decreased caregiver burden. The child’s GMFCS level and the MMAS did not change. Further data collection related to treating children with spasticity using IMES is indicated to validate this type of TX with this patient population.

Neuropathic pain (NP), which is difficult to treat, remains a heavy burden for both individuals and society. The efficacy of current treatments is insufficient. The pathophysiology of NP is still not fully elucidated, and there is a need to explore new therapeutic targets to develop more effective treatment strategies. Recent studies showed that thrombospondin 4 (TSP4) protein expression is increased in the spinal cord following nervous system injury and that blocking or inhibiting this increase improves NP. In this review, it has been aimed to present the evidence for the role of TSP4 in the mechanisms of NP development and to evaluate the therapeutic potential of TSP4 blockade in the treatment of NP.

Myasthenia gravis (MG) is a rare auto-immune neuromuscular junction (NMJ) disorder which is caused by formation of autoantibodies and destruction of NMJ components. The MG diagnosis is based on the symptoms, autoantibodies detection and paraclinical tests. Given that MG patients have so many differential diagnosis and various medication responses, choosing an accurate diagnosis and the therapy plan in MG is challenging. According to the studies, there are the immunologic, genetic, microRNAs, gut microbiome, and other established or newly proposed biomarkers for diagnosis and prognosis of MG. More studies are needed to provide better collection of biomarkers in MG patients and evaluate their role in MG pathology.

Different stressors can elicit neuroinflammatory responses modulated by innate immunity receptors, such as the family of Toll-like receptors (TLRs). The TLR4, a pattern recognition receptor (PRR), is involved in many diseases, such as inflammatory and central nervous system (CNS) diseases. Stress exposure can regulate the expression of PRRs, including TLR4, in the brain of animals, especially in the hippocampus and prefrontal cortex. Moreover, TLR4 modulates behavior and neuroinflammatory responses in the brain. In addition, to TLR4, the endocannabinoid (eCB) system plays a role in stress response and immunity, acting as a regulatory, stress-buffer system. This system is involved in many TLRs-mediated immune responses, such as microglia activation. Therefore, pharmacological approaches targeting the eCB system could modulate neuroinflammatory responses to stress by interfering with the TLR4 pathway. Although the connection between TLR4, stress, and neuroinflammation is well documented, almost no pre-clinical studies investigate the possible direct relationship between TLR4, behavior, stress, and the eCB system. Studies exploring the relationship between stress, neuroinflammation, TLR4, and the eCB system were searched using Pubmed, Web of Science, and Embase databases. Based on this search, this review is focused on the involvement of TLR4 receptors and signaling in neuroinflammation and the behavioral consequences of stress exposure. Moreover, evidence of the eCB system modulating TLR4-mediated responses was brought to the attention, pointing out a possible regulatory role of these responses by eCBs in behavior changes related to mood disorders.