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We present the case of a male in his mid-30s with a progressive complex neurological phenotype primarily characterised by levodopa-responsive parkinsonism with motor fluctuations as well as gait ataxia, peripheral neuropathy and finally also spastic paraplegia. Genetic analysis identified a novel heterozygous variant in the KIF5A gene: c.937G>A (p.Glu313Lys). This variant is genetically classified as likely pathogenic. Other pathogenic mutations in the KIF5A gene are associated with hereditary spastic paraplegia type 10, Charcot-Marie-Tooth disease type 2 and amyotrophic lateral sclerosis. We discuss the clinical, genetic and prognostic implications of this finding.

A man in his 70s presented with a subacute akinetic–rigid syndrome consistent with secondary parkinsonism, characterised by axial rigidity, bradykinesia, hypophonia, gait initiation failure and constitutional symptoms. MRI demonstrated symmetrical T2/FLAIR hyperintensities involving the brainstem, diencephalon and dentate nuclei. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis, markedly elevated protein and low glucose, together with increased CXCL13 levels (exact quantitative value unavailable from the external laboratory report). Serum Borrelia IgG was positive and confirmed by western blot. No alternative infectious, autoimmune or neoplastic aetiology was identified. The overall picture supported a diagnosis of probable late neuroborreliosis according to EFNS criteria. Treatment with intravenous ceftriaxone followed by oral doxycycline resulted in rapid improvement. At 6-month follow-up, he was clinically asymptomatic and brain MRI demonstrated complete radiological resolution. This case highlights neuroborreliosis as an uncommon but reversible cause of secondary parkinsonism/parkinsonism mimic and underscores the diagnostic relevance of its distinctive imaging pattern.

BackgroundSpinocerebellar ataxia type 28 (SCA28) is a dominantly inherited neurodegenerative disease caused by pathogenic variants in AFG3L2. The AFG3L2 protein is a subunit of mitochondrial m-AAA complexes involved in protein quality control. Objective of this study was to determine the molecular mechanisms of SCA28, which has eluded characterisation to date.MethodsWe derived SCA28 patient fibroblasts carrying different pathogenic variants in the AFG3L2 proteolytic domain (missense: the newly identified p.F664S and p.M666T, p.G671R, p.Y689H and a truncating frameshift p.L556fs) and analysed multiple aspects of mitochondrial physiology. As reference of residual m-AAA activity, we included SPAX5 patient fibroblasts with homozygous p.Y616C pathogenic variant, AFG3L2+/− HEK293 T cells by CRISPR/Cas9-genome editing and Afg3l2 −/− murine fibroblasts.ResultsWe found that SCA28 cells carrying missense changes have normal levels of assembled m-AAA complexes, while the cells with a truncating pathogenic variant had only half of this amount. We disclosed inefficient mitochondrial fusion in SCA28 cells caused by increased OPA1 processing operated by hyperactivated OMA1. Notably, we found altered mitochondrial proteostasis to be the trigger of OMA1 activation in SCA28 cells, with pharmacological attenuation of mitochondrial protein synthesis resulting in stabilised levels of OMA1 and OPA1 long forms, which rescued mitochondrial fusion efficiency. Secondary to altered mitochondrial morphology, mitochondrial calcium uptake resulted decreased in SCA28 cells.ConclusionOur data identify the earliest events in SCA28 pathogenesis and open new perspectives for therapy. By identifying similar mitochondrial phenotypes between SCA28 cells and AFG3L2+/− cells, our results support haploinsufficiency as the mechanism for the studied pathogenic variants.

Choreo-acanthocytosis (hAc) is an autosomal-recessive, neurodegenerative disorder, often presenting as movement disorder, seizures and behavioural changes. This case report describes a male patient who presented with progressive movement disorder, long-standing seizures and cognitive impairment. Neurological examination and neuroimaging revealed features suspicious for basal ganglia degeneration. Routine metabolic and infectious investigations were negative. Genetic testing identified a likely pathogenic VPS13A variant (c.799C>T, p.Arg267Ter), a rare genetic mutation associated with ChAc. This report highlights the complexities of diagnosis, differential considerations, the importance of genetic testing in atypical movement disorders, therapeutic strategies,and the detrimental impact of the VPS13A gene mutation on the patient’s quality of life. This case also tries to expand the known mutational spectrum of the VPS13A gene and its varied clinical presentation.

A previously fit and well patient in his 70s presented after recurrent transient loss of consciousness following dinner with alcohol consumption. Each event has been preceded by several minutes of transient abnormal posture and gait. More specifically, there were several minutes of stiffening of legs, shuffling gait and gait ataxia. Initial clinic investigations, including ECG, echocardiogram, CT and MRI head scans, vestibular tests and biochemistry for vitamins and electrolytes, proved inconclusive. However, a positive tilt table test demonstrated severe orthostatic hypotension (OH) with loss of consciousness.Acute alcohol consumption worsens OH, and prolonged hypotension can potentiate cerebral hypoperfusion leading to syncopal events. Compromise to posterior circulation during these events may cause transient gait abnormalities. Such cases have not been widely documented in the literature. Transient gait disturbance in syncope remains underexplored. Further research and documentation are needed, informing better diagnostic and management strategies.

A woman in her 70s presented with approximately 2 years of sudden-onset gait and cognitive problems. She had been diagnosed with normal pressure hydrocephalus (NPH) and underwent ventriculoperitoneal shunt (VPS) placement 1 year prior. Before VPS placement, brain imaging showed ventriculomegaly and chronic infarction of the right putamen and claustrum. A lumbar drain trial resulted in modest improvement of gait dysfunction. She underwent VPS placement for suspected NPH, but her symptoms remained unchanged. Examination revealed mild cognitive impairment, left-sided and lower body predominant parkinsonism, as well as disproportionately prominent postural instability. Gait analysis showed increased gait variability, reduced velocity and shortened step length bilaterally. Motor and gait abnormalities did not change after administration of levodopa. Her symptoms have remained stable for up to 52 months since symptom onset. We postulate that the infarction affecting the right putamen and claustrum could have led to a higher-level gait disorder mimicking NPH.