Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy presenting as severe herniated nucleus pulposus: A case report

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is the most common inher ited cerebral microangiopathy. Its clinical features include recurrent central nervous system symptoms—including lacunar stroke, migraine, psychiatric disturbance, acute reversible encephalopathy, and cognitive impairment. We report a case of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in a patient presenting with severe low back pain and a herniated nucleus pulposus. A 45-year-old female patient with a prior history of right-sid ed sciatic pain, hypoesthesia, and paresthesia in the right S1 sensory dermatome was referred after back surgery because of persistent low back pain and a spastic gait abnormality. Imaging revealed a right protruding disc herniation of L5/S1 with right S1 nerve root compression and right posterior disc bulging at L4/5 with foraminal stenosis and disc degenera -tion, for which she underwent surgery. After surgery, she experienced mild sciatica, an antalgic limping gait with foot-drag -ging, and progressive motor weakness. Her family history was significant for a parent and sibling affected by stroke. The diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy was estab lished by polymerase chain reaction sequencing, which showed a mutated exon 11 of NOTCH3 on chromosome 19. Clini cians should assess patients with non-specific extra-central nervous system symptoms or atypical courses for potential underlying diseases.


IntroduCtIon
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CA-DASIL) is the most common dominantly inherited cerebral small vessel disease [1,2]. CADASIL is caused by pathogenic mutations clustered in exons 2-23 of the NOTCH3 gene on chromosome 19 and has four distinct cardinal manifestations: stroke, migraine headache with aura, psychiatric disturbance and cognitive decline [1,3]. However, central nervous system (CNS) and peripheral neurological symptoms and neuromuscular involvement have been reported in patients with CADASIL [2][3][4][5], but not herniated lumbar discs accompanied by severe low back pain. Here, we describe the case of a 45-year-old female with confirmed CADASIL who presented with low back pain and disc herniation which were manifest as extra-CNS manifestations.

CASe PreSentAtIon
A 45-year-old female patient presented with an 8-year history of right-sided sciatic pain, hypoesthe-sia and paresthesia in the right S1 sensory dermatome. She was referred to our service for persistent low back pain and gradual development of a spastic gait abnormality after back surgery. Lumbar magnetic resonance imaging (MRI) revealed right protruding disc herniation of L5/S1 with right S1 nerve root compression and right posterior disc bulging at L4/5 with foraminal stenosis and disc degeneration ( Figure 1). FIGure 1. Lumbar magnetic resonance imaging reveals mild focal protruding disc herniation with mild inferior migration at the right posterolateral side of L5/S1, causing (a-c) right S1 nerve root compression and (d-f) posterior disc bulging at L4/5.
Eight months before presentation, she underwent partial hemilaminectomy, ligamentum flavectomy, foraminotomy at the right L5/S1 and L4/5 levels, and a discectomy at the right L5/S1 level. During surgery, a thecal sac, S1 root compression caused by rupture of L5/S1 disc (non-traumatic), and canal stenosis due to hypertrophy of the L4/5 ligamentum flavum were noted. Her pain, numbness, and hypoesthesia in the right anterior thigh improved after surgery. However, she experienced mild sciatica, an antalgic limping gait with foot-dragging, progressive motor weakness (Medical Research Council grade 4), and spastic gait disturbance in the right leg.
She was being administered antihypertensive medication (amlodipine 5 mg once per day) for 11 years, and her blood pressure was normal. Her family history revealed a brother who sustained a minor stroke with slurred speech at age 41. Her mother died of a major stroke at age 56. The patient had no history of migraine, baldness, epileptic seizure, cognitive impairment (Korean version of Mini-Mental Status Examination: 30/30) [6], or major psychiatric problems. The results of routine blood tests and autoimmune markers as anticardiolipin, lupus anticoagulant, and anti-neutrophil cytoplastic antibody were within normal limits. Electrodiagnostic studies revealed right lower lumbar and lumbosacral radiculopathy. A brain MRI revealed multiple chronic infarctions and severe chronic periventricular ischemic white matter changes (Figure 2), while the results of magnetic resonance angiography were normal. She and her brother showed the same missense mutation c.1819C>T (pArg607Cys, heterozygote) on exon 11 of NOTCH3 on chromosome 19 (19p13.2-p13.1) on polymerase chain reaction sequencing studies and were diagnosed with CADASIL. After receiving neural block intervention and prescription antiplatelets (clopidogrel 75 mg per day), antidepressants (escitalopram oxalate 10 mg per day), antispastic medica- tions (baclofen 20 mg, twice a day), and rehabilitation therapy, she could walk comfortably with decreased spasticity and pain.

dISCuSSIon
We report an unusual case of CADASIL in a patient presenting with severe low back pain and herniated nucleus pulposus following an atypical postsurgical course and without a classic CADASIL symptom profile. While recent studies have reported an extra-CNS involvement in CADASIL [2][3][4][5], no reports have demonstrated an association of CA-DASIL with severe low back pain, spondylosis or disc herniation, or nodular thickening of the posterior longitudinal ligament. One case reported an association with back pain and alopecia [7].
The possibility of CADASIL with extra-CNS symptoms is low, and its pathogenic interpretation difficult. The classic symptoms seen in cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). CARASIL is a less-common, inherited, cerebral, small-vessel disease. It has characteristic extra-CNS symptoms, including premature baldness/alopecia (90% of pa-