Focal CNS vasculitis masquerading as new-onset focal aware seizures

Abstract

Primary angiitis of the central nervous system (PACNS) is an autoimmune disease with myriad presentations in the form of headache, focal neurological deficits, seizures and rapid cognitive decline. Predilection or isolated and recurrent involvement of one hemisphere is rarely described in literature. This leads to low clinical suspicion and often delayed diagnosis of PACNS, if clinical and radiological involvement is focal. We describe the case of a young man presenting with new-onset focal seizures with imaging suggestive of focal involvement and the brain biopsy clinched an early diagnosis. The 1-year follow-up showed clinical and radiological resolution.

Background

Focal cerebral vasculitis is a rare disease with varied presentations. There is a paucity of literature about pathophysiology, clinical presentation, treatment and outcome of this entity. We present a case of an adult man with focal cerebral vasculitis presenting with focal aware sensory seizures.

Case presentation

A 40-year-old man presented to our outpatient clinic with six episodes of focal aware sensory seizure involving the left half of face for 5 months. Each episode had been brief lasting for 1–2 min except the last which occurred 1 week ago. The seizure lasted for almost 5 hours. There was no impairment of consciousness or secondary generalisation in any of the episode. There was no history of fever, headache, rash, oral ulcer or joint pain. He had no other comorbidities. He was admitted to our centre for evaluation of the same. Clinical examination was normal. Specifically, there was no sensory loss over the left face.

Investigations

Haematological and biochemical parameters were within normal limits. Erythrocyte sedimentation rate was 26 mm in 1 hour (normal range 0.00–20.00) and C reactive protein was 4.58 (normal range <5.0 mg/L). Antinuclear antibody, extractable nuclear antigens antibody, antineutrophil cytoplasmic antibodies, anticardiolipin antibody and antidouble-stranded DNA were negative. Serum ACE level and 24-hour urinary protein were normal. Cerebrospinal fluid examination was negative for infection or neoplasm. Interictal electroencephalogram was normal. Contrast-enhanced MRI of the brain showed irregular T2/FLAIR(Fluid-attenuated inversion recovery) hyperintensities in subcortical white matter of left parietaltemporal lobe. On postcontrast study, linear and punctate pattern of enhancement was seen in the lesions. Multiple foci of blooming were noted along the vessels in the left parietotemporal lobe (figure 1A–D). Digital subtraction angiography of cerebral vessels revealed focal puddling of contrast in the left MCA(Middle Cerebral artery) territory, consistent with vasculitis. Brain biopsy was performed, which revealed the presence of perivascular epithelioid cell granuloma consistent with the diagnosis of granulomatous angiitis (figure 2A–D).

Figure 1.

(A) T2 FLAIR(Fluid-attenuated inversion recovery) image showing hyperintense lesion in left parietal area (arrow), (B) SWI image showing blooming in the left parietal area (arrow), (C) contrast enhancement of the lesion (arrow), (D) coronal section depicting the contrast enhancement (arrow), (E) follow-up MRI 1 year showing resolution of the lesion in T2 FLAIR, (F) SWI image, (G) T1 with contrast axial and (H) coronal image. SWI, susceptibility-weighted imaging.

Figure 2.

(A, B) H&E (×20) shows transmural inflammation around a vessel with granuloma formation. (C, D) H&E (×40) shows perivascular granuloma formation with epithelioid histiocytes and mononuclear inflammatory infiltrate comprising lymphocytes.

Treatment

The patient was treated with 5 days of intravenous methylprednisolone, followed by maintenance immunosuppression with oral steroids and mycophenolate mofetil. There was complete resolution of seizures without development of any new systemic or neurological symptoms.

Outcome and follow-up

MRI brain was repeated after 1 year showed decrease in T2/FLAIR hyperintensities and enhancement in the left parietotemporal lobe with persistent blooming foci in the left parietotemporal lobe (figure 1E–H).

Discussion

Primary central nervous system (CNS) vasculitis predominantly affects small-sized and medium-sized arteries of the brain parenchyma, spinal cord and leptomeninges. There are protean manifestations of primary CNS vasculitis. In a study of Mayo clinic cohort of adult-onset primary CNS vasculitis, the most common clinical presentation includes headache and cognitive impairment, followed by stroke and visual symptoms.¹ Other less common presentations include cranial neuropathies, ataxia, seizures, intracranial haemorrhage, parkinsonism and coma. Our case presented with new-onset focal seizures, with unusual imaging findings, which led to the definitive diagnosis on biopsy. It is important to rule out other conditions presenting with sensory seizure such as infection, autoimmune diseases, vascular, inflammatory and paraneoplastic causes. In a systematic review, 137/310 patients had hemiparesis and 47/160 had unilateral numbness of skin, so focal deficit is not uncommon.² However, in the study by Salvarni et al, bilateral vasculitis was demonstrated in 95.6% cases.¹ Since unilateral or focal presentation of primary CNS vasculitis is very rare, every single addition would be useful in expanding the knowledge about this entity.³ Also referred to as unilateral relapsing primary angiitis of the CNS, the earlier cases were suggested to have an overlap with adult onset Rasmussen’s encephalitis,⁴ although series of case reports published later identified this as a distinct and rare subtype of primary CNS vasculitis.^{5 6} Absence of progression of hemiatrophy, persistence of contrast enhancement and blooming on susceptibility-weighted imaging on MRI brain may help in differentiating the two conditions. So far, seven cases have been reported in literature, but none from India.³ Out of seven cases reported, seizure was presenting symptoms in all but six cases had other neurological manifestations also like focal motor or sensory deficit and cognitive impairment. Besides, all patients had multiple relapses.³ In our case, only seizure was present without any other deficit and there was good remission with treatment without any relapse. Since, the diagnosis was picked up in the index clinical event, our case suggests that early diagnosis may alter the natural history of the disease and prevent cognitive disturbances, as has been reported in earlier cases with delayed diagnosis.⁴ The involvement of only one hemisphere in rare cases of primary CNS vasculitis is not clear and may be related to nature of disease, different development of one hemisphere during embryogenesis or hemispheric differences in immune response mechanisms.³ Various mechanisms such as antigenic basis, handedness, asymmetrical vessel distribution, lymphatic drainage have been thought to be responsible for unilaterality of primary CNS vasculitis. However, hemispheric asymmetry in immune reactivity might be more likely to be the cause rather than any antigenic or structural differences between them.^{7 8} We also emphasise on mandatory exclusion of other possible clinical and radiological mimickers such as secondary vasculitis and space-occupying lesions (SOLs), primary CNS lymphoma.⁹ The unihemispheric involvement makes the commoner differentials like Rasmussen encephalitis and SOLs more likely in clinical settings. Hence, a brain biopsy is a vital investigation. The biopsy not only aids in definitive diagnosis and prognosis, but also helps in preventing false assurance to the patient, in case steroids are started empirically, and the patient worsens, in case of an SOL.

Learning points.

• Cerebral vasculitis can present with only seizure or headache without any focal deficit.

• Although bilateral, cerebral vasculitis can have focal presentation.

• Blooming on susceptibility-weighted imaging, T2/FLAIR hyperintensities and linear and punctate pattern of enhancement should lead to suspicion of cerebral vasculitis.

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