Hereditary spastic paraplegia (HSP) comprises a clinically and genetically diverse group of inherited neurodegenerative disorders unified by slowly progressive, usually symmetrical lower-limb spasticity secondary to corticospinal tract degeneration. For practising neurologists, the first step is recognising when a presentation is consistent with HSP and when it is not, and then carefully excluding treatable causes. We outline a pragmatic approach to assessing HSP, highlighting the broad clinical spectrum, 'red flags' that should trigger re-evaluation and the common acquired and genetic mimics. We summarise the relevant clinical and supportive investigations that can narrow the differential diagnosis. We also discuss the strengths and limitations of contemporary genetic testing. Finally, we focus on practical management: multidisciplinary care, spasticity treatments, and proactive recognition and management of additional symptoms outside of spasticity.

Ischemic gastritis (IG) and ischemic duodenitis (ID) are rare due to the extensive anastomotic vascular supply arising from the celiac trunk. Profound splanchnic hypoperfusion is required to induce a clinically significant ischemic insult. Etiologies typically include systemic hypotension, vasculitis, or thromboembolism. Patients with IG/ID often face high morbidity and mortality given the severity of ischemia required to induce extensive mucosal damage, leaving clinicians to balance prolonged bowel rest and early enteral feeding. We present the case of an 18-year-old man with spastic quadriplegic cerebral palsy and developmental delay who developed severe IG/ID in the setting of severe hemorrhagic shock. He presented to our institution with hemodynamic instability, profound anemia, and signs of upper gastrointestinal bleeding. Endoscopic evaluation found the patient to have severe IG/ID necessitating prolonged bowel rest and total parenteral nutrition (TPN). After evidence of mucosal recovery on surveillance endoscopy, he was gradually transitioned from TPN to enteral nutrition and successfully discharged to a long-term care facility. This report describes the successful reintroduction of enteral feeding in a patient with severe IG/ID after prolonged bowel rest. The use of surveillance endoscopy to guide the gradual reintroduction of enteral feeding, alongside careful TPN weaning, allowed for the successful discharge of a patient with IG/ID, a condition associated with poor outcomes.

Fatty acid hydroxylase-associated neurodegeneration (FAHN) is an ultra-rare neurological disorder caused by a mutation in the FA2H gene. Defective production of this gene leads to abnormal myelin formation, which subsequently causes neurodegeneration and brain iron accumulation. This case report presents the case of a 7-year-old boy from Pakistan who was born to consanguineous parents. The initial symptom presented at two and a half years of age with seizures. His clinical course progressively worsened, manifesting as gait disturbances, dystonia, and regression of milestones. By the age of 7, he was unable to walk without support. On examination, the patient had a spastic diplegic gait with plantarflexion contracture in both lower limbs. Brain Magnetic Resonance Imaging (MRI) findings reported abnormal T2-weighted hyperintensities, predominantly involving the parietal white matter, which is suggestive of FAHN. Finally, the diagnosis was confirmed by genetic analysis with the identification of a strong homozygous c.704G>A (p.Arg235 His) missense mutation in the FA2H gene.

Hereditary spastic paraplegia (HSP) is a heterogeneous group of genetically determined diseases, characterized by progressive spastic paraparesis of the lower limbs, associated with degeneration of the corticospinal tract and the posterior column of the spinal cord. Currently known to be about 70 genes are involved in HSP, though new potentially pathogenic variants are being reported regularly. Almost all patterns of inheritance like autosomal dominant, autosomal recessive, X-linked, and mitochondrial have been found in families of HSP patients. However, autosomal recessive form, hereditary spastic paraplegia type 11 is the most common one. We presented a case of an 18-year-old woman, with no significant medical history and without known consanguinity, presented with a 2-year history of sub-acute onset and slowly progressing weakness and stiffness in both lower limbs and difficulty in walking and finally diagnosed as a Hereditary Spastic Paraplegia 11. Genetic analysis by whole-exome sequencing on the Illumina Novaseq 6000 NGS Platform was done and indicated homozygous variations in exon 4 of gene SPG11(chr15:g.44657230_44657231delAT): the c733_734del p (Met245ValfsTer2) variant on the allele. Here, we describe the clinical, radiological, and genetic presentation of Spastic paraplegia 11 (SPG11) through a report of a case and compare it with previously reported SPG11 cases in the literature.

Acute promyelocytic leukemia (APL) is a hematologic emergency characterized by a high risk of coagulopathy that can manifest with both severe bleeding and thrombotic events, including ischemic stroke. However, its initial presentation as large vessel arterial thrombosis is infrequent and potentially lethal. We report the case of a previously healthy 15-year-old female referred for suspected left frontal ischemic stroke with right spastic hemiplegia and expressive aphasia. One week earlier, she had presented with headache, nausea and transient episodes of paresthesias and weakness of the right hand and foot. Laboratory studies revealed bicytopenia (leukopenia and anemia), hypofibrinogenemia and elevated D-dimer. Imaging studies showed a subacute infarct in the left caudate nucleus and recent ischemia in the frontal cortex with complete occlusion of the left internal carotid artery. Bone marrow aspirate showed blast cells with Auer rods and strong positivity for myeloperoxidase. Flow cytometry revealed 41,2 % of cells with a phenotype compatible with promyelocytes, PML::RARA fusión gene was confirmed by molecular and cytogenetic studies. Immediate treatment with all-trans retinoic acid (ATRA), corticosteroids, and hemostatic support was initiated. Subsequently, the patient presented with a new occipital infarction and was started on anticoagulant therapy. She did well with motor and speech recovery. This case highlights the importance of considering APL as an underlying etiology of arterial thrombotic events in adolescents with cytopenias and coagulopathy, especially in the presence of major vessel occlusion, where early diagnosis and timely treatment are essential to reduce morbidity and mortality.

Defective feedback inhibition of serine palmitoyltransferase (SPT) caused by pathogenic SPTSSA variants underlies childhood-onset complex hereditary spastic paraplegia, yet the developmental timing and therapeutic reversibility of sphingolipid dysregulation remain unclear. We generated a knock-in mouse carrying the disease-associated SptssaT51I variant and show that heterozygous animals exhibit preserved intrinsic SPT activity but impaired ORMDL-mediated regulation, leading to sustained elevation of bioactive sphingolipid intermediates that peak during postnatal myelination. Although gross myelin formation was initially maintained, excess sphingolipid flux rendered oligodendrocytes and neurons selectively vulnerable. Dietary L-serine, which augments SPT substrate availability, amplified sphingolipid accumulation in mutant but not wild-type mice, unmasking progressive spasticity, axonal injury, myelin ultrastructural defects, and, when administered during early postnatal development, severe pulmonary pathology likely responsible for lethality. Pharmacologic SPT inhibition with myriocin normalized sphingolipid synthesis, prevented serine-induced lethality, and reversed neurological and metabolic abnormalities. Translating these findings, treatment of a child with SPTSSA-T51I-associated complex hereditary spastic paraplegia using the FDA approved SPT inhibitor D-Cycloserine resulted in sustained improvement in spasticity, reduced baclofen requirement, and decreased plasma levels of neurofilament light chain (NFL). These data define dysregulated sphingolipid biosynthesis as a developmentally and metabolically sensitive driver of neurodegeneration and suggest SPT inhibition as a mechanistically grounded therapeutic strategy.

Vacuolar protein sorting 16 (VPS16) functions in endolysosomal trafficking. Biallelic VPS16 variants cause a mucopolysaccharidosis-like syndrome reported in only four patients, with neurological involvement ranging from mild developmental delay to severe impairment with epilepsy and pyramidal signs. We report an additional patient biallelic for VPS16 NM_022575.4:c.2272-18 C > A, with profound developmental delay, early-onset epilepsy, and spasticity. Multisystem involvement included recurrent infections, neutropenia, serosal effusions, and tubular proteinuria. Brain MRI showed white-matter abnormalities, progressive cerebral and cerebellar atrophy, and symmetric signal changes in the globus pallidus and substantia nigra, suggestive of iron deposition, further expanding the neurological spectrum of this disorder.

Diffuse idiopathic skeletal hyperostosis (DISH) is a non-inflammatory condition characterized by ossification of spinal ligaments, commonly affecting elderly individuals. While often asymptomatic, it may present severe neurological deficits due to spinal cord compression. We report what is believed to be the first documented case of DISH presenting with cervical myelopathy in Sudan. A 73-year-old diabetic man presented with progressive weakness in all limbs, accompanied by neck and back pain. Neurological examination revealed spastic quadriparesis, sensory loss to proprioception and vibration, and signs consistent with cervical myelopathy. No bowel or bladder involvement was reported. Imaging studies including CT and MRI of the spine demonstrated ossification of the anterior and posterior longitudinal ligaments throughout the cervical region, with severe spinal canal stenosis at C5-C7. Additional lumbar stenosis due to ligamentum flavum hypertrophy was also noted. A diagnosis of DISH with cervical myelopathy and lumbar stenosis was made. Surgical decompression was planned; however, the patient died unexpectedly before the planned intervention. DISH with cervical myelopathy is rarely encountered in clinical practice and has traditionally been considered more prevalent among Asian populations; however, we report what is, to our knowledge, the first documented case of DISH with cervical myelopathy in Sudan. This case report underscores the importance of early recognition of DISH in settings where it is rarely reported, in order to improve clinical outcomes. Furthermore, this case report highlights the need for further epidemiological and clinical studies in the country to assess the prevalence, risk factors, and management outcomes associated with this underrecognized rheumatologic disorder.