Cervical Cord Hemorrhage in Cerebral Cavernous Malformations

Dear Editor, Cavernous malformations are vascular malformations of the central nervous system, with the lesions comprising clusters of abnormal small blood vessels that are mostly detected intracranially. Mutations in KRIT1, CCM2, and PDCD10 have been found to cause cerebral cavernous malformations (CCMs). CCM proteins can bind different molecules such as scaffolding proteins and kinases, and form a CCM signaling complex (CSC). Mutant CCM proteins impair the function of the CSC and cause endothelial barrier dysfunction and hyperpermeable blood vessels.1 Twenty percent of CCMs are familial cases with an autosomal dominant pattern, with incomplete penetrance and variable expressivity. Mutations in KRIT1, CCM2, and PDCD10 account for 50%, 20%, and 10% of familial cases, respectively.1 Most cases with widespread lesions are hereditary, and cases with isolated lesions may exhibit mosaicism.2 The clinical presentation varies with the location, number, and size of the lesions. Recurrent hemorrhage in the lesions causes neurological deficits in CCMs patients. Intramedullary spinal cavernous malformations (ISCMs) are rare, accounting for 5–12% of all intraspinal vascular malformations.3 However, the prevalence of ISCMs is high (about 70%) in cases of familial CCMs and is positively correlated with the age at onset and number of lesions.4 Here we report on a case of ISCMs presenting with hemiplegia, including providing imaging, pathological, and genetic data. A 62-year-old female complained of numbness and a paroxysmal sense of discharge, weakness in the upper left limb for 8 months, and progressive weakness in the lower left limb for 4 months. Pain in the waist had resulted in schwannoma of the left lumbar nerve root being diagnosed 4 years previously. Resection of the schwannoma produced the sequela of numbness in her left lower limb. At the current presentation, a neurological examination revealed that the strength of the left upper limb was Medical Research Council scale (MRC) grade 3/4, with distal muscles more severely affected than proximal muscles. The strength of the left lower limb was MRC grade 4. The strength of the right extremities was normal, and ataxia was not found. Analgesia was revealed in the upper left limb. Hypesthesia was found below the left knee, which was presumed to be a remnant sign from the schwannoma resection in the lumbar nerve root 4 years previously. Her proprioception was normal. Tendon reflexes were active except for Achilles reflexes. Hoffman and Babinski signs were positive bilaterally, and more prominent in the left. Brain susceptibility-weighted MRI showed diffused lesions consistent with CCMs in the cerebral hemispheres, cerebellum, and brain stem (Fig. 1A-C). A physical examination indicated the damage of the cervical spinal cord, and so we performed the cervical MRI, which revealed oval intramedullary mixed signals (about 0.9 cm × 0.7 cm × 1.9 cm), predominantly on the left side at the fifth cervical vertebra level (Fig. 1D-F). Whole-exome sequencing identified that the patient carried a mutation in KRIT1, which was confirmed by Sanger sequencing. No mutation was detected in either CCM2 or PDCD10. Combined with the genetic analysis, CCMs caused by a known KRIT1 mutation Zhanjun Wang Hao Wu Yueshan Piao Chaodong Wang