50.1 Case Description
50.1.1 Clinical Presentation
A 21-year-old male presented with confusion, nausea, vomiting and severe headache, as well as abdominal pain and mild right-sided weakness. The onset of symptoms was not witnessed, as he was found at home by his parents, and was last seen well earlier the same day. In the emergency room, his presentation activated the acute stroke protocol. Examination revealed a left hemispheric syndrome with expressive and receptive language deficits, mild hemiparesis, and inattention. He was unable to answer questions but could follow simple commands. He also had dysconjugate gaze with double vision to rightward gaze.
Collateral history from his family revealed that he had been admitted to another hospital 3 weeks previously with a similar presentation. At that time, he had developed gradual onset of confusion, with right-sided paresthesia, followed by headache and abdominal pain. His clinical status had progressed to stupor with severe right-sided weakness, ongoing headache, nausea and vomiting. Over the course of 24 to 48 hours, he had gradually recovered to baseline. MRI of the brain at that time, according to his family, had not shown significant abnormality. Subsequent records from the previous admission were obtained which showed he had undergone lumbar puncture. Cerebrospinal fluid (CSF) analysis revealed a raised white cell count (WBC; 173/µL), mildly elevated protein (71 mg/dL), and normal glucose level.
The patient had also experienced recent onset of headaches with nausea, vomiting, photophobia and phonophobia, and abdominal pain, with three episodes over the preceding 3 months. He also had a history of depression. Otherwise, he was healthy, with no comorbidities, no cardiovascular risk factors, and no relevant family history. The only regular preadmission medication was escitalopram 10 mg daily.
50.1.2 Imaging Workup and Investigations
Noncontrast CT (NCCT), CTA, MRI, MRA, MR perfusion (MRP), and digital subtraction angiography were all performed on the day of admission.
NCCT of the brain was performed initially and appeared normal, with no evidence of infarction, hyperdense vessel sign, or hemorrhage (Fig. 50.1a). No intracranial proximal large artery occlusion was seen on intracranial CTA (Fig. 50.1b). Note was however made of generalized paucity of distal arterial branches over the left hemisphere compared to the contralateral right side (Fig. 50.1c–e).
MRI demonstrated generalized hyperintensity throughout the left hemispheric cortex on T2 FLAIR and diffusion-weighted imaging, with subtle reduced apparent diffusion coefficient (ADC) value in the cortex of the left parietal region (Fig. 50.2a–c). MRP demonstrated reduced cerebral blood flow (CBF) throughout the left cerebral hemisphere compared to the contralateral side (Fig. 50.2d). Contrast-enhanced MRA of the extracranial arterial system showed no upstream arterial lesion to explain this, with normal appearance of the extracranial arteries (Fig. 50.2e). There was no evidence of leptomeningeal enhancement or abnormal enhancement elsewhere on postgadolinium imaging of the brain (not shown).
Catheter angiography was performed, demonstrating a wedge-shaped area of mildly delayed arteriovenous contrast transit time involving the posterior left middle cerebral artery (MCA) territory (Fig. 50.3a, b). There was no evidence of arterial irregularity or areas of stenosis to suggest a vasculitis or other vascular abnormality. The remainder of the examination was unremarkable. The site of abnormality correlated to the site of maximum abnormality on the patients’ previous CTA and MRI examinations.
EEG showed some slowing in the left frontotemporal region but no epileptiform discharges. This was deemed mildly abnormal.
Lumbar puncture was performed. CSF analysis again revealed elevated white cell count (WBC 35/µL (95% lymphocytes), raised protein (47 mg/dL), and normal glucose. CSF culture was negative and viral culture was negative for Herpes Simplex Virus 1 and 2 as well as negative for varicella zoster and EBV. CSF cytology was negative for malignancy, although it did demonstrate chronic inflammation that included small T lymphocytes. There was no evidence of a lymphoproliferative disorder.
Porphyria screen was negative. Liver enzymes were normal. Testing for hypercoagulable state revealed no abnormalities. A molecular screen was performed for any genetic abnormality, with no significant abnormality revealed.
HaNDL—Syndrome of transient Headache and Neurological Deficits with cerebrospinal fluid Lymphocytosis.
50.1.4 Treatment and Follow-up
The symptoms and signs gradually started to resolve within the first 6 hours of hospitalization, with just subtle parietal symptoms and mild language difficulties remaining by day 2 of admission. He subsequently made a complete recovery. He was commenced on verapamil, prior to discharge, as a prophylactic agent to prevent future headaches. Antiplatelet medication was not administered. Follow-up MRI 1 month following presentation was normal (Fig. 50.4). At 1-year clinic follow-up, he remained asymptomatic with no further episodes and no further headaches.
50.2 Companion Case
50.2.1 Clinical Presentation
An 18-year-old female presented to the emergency room with a moderate to severe throbbing headache, of onset over hours, in a frontal distribution with radiation to the left ear. This was associated with nausea and vomiting as well as photophobia and phonophobia. There was no history of fever, rash or neck stiffness. There was no recent travel. Her vaccinations were up to date. She was discharged from the emergency room with a diagnosis of migraine.
Following discharge, her headaches remained intermittently present; 2 days later, she developed a fever, prompting her to again visit the hospital. A lumbar puncture showed 500 × 106 leukocytes/mL, with 96% lymphocytes. Cultures and viral studies were negative. She was treated for presumed aseptic meningitis with intravenous Acyclovir. She improved markedly during admission and was discharged on oral Acyclovir.
She continued to improve, with only a mild, intermittent residual headache. However, 2 weeks later, she had a relapse, with severe headache, nausea, vomiting, and fatigue. Her father noted her speech to be incoherent. She also had two episodes of arm numbness, one on the right and one bilateral. She was again taken to the emergency department and examination was notable for lethargy, drowsiness, and fluent aphasia.
50.2.2 Imaging Workup and Investigations
A lumbar puncture was again performed, revealing 513 × 106 leukocytes/mL with 99% lymphocytes, 1% monocytes, and no visualized Mollaret cells. Protein was 1.06 g/L and glucose was 3.6 mmol/L. Cytology showed reactive lymphocytes. Viral polymerase chain reaction including herpes simplex virus and varicella zoster virus were negative. Bacterial and fungal cultures and cultures for acid fast bacilli were also all negative. HIV testing was also negative, as were screening autoimmune studies. Finally, a contrast-enhanced MRI and MRA were all found to be normal.