1. Neurology Case Presentation Scott M. Shorten, MD PGY-3

2. Right-handed man CC: right facial droop, right arm and leg tingling and weakness

3. HPI recurrent drooping of the right face started 1.5 yrs ago without clear precipitant multiple times per day and while asleep, no warning, no trigger Average 30 minutes (5 min-2 hours), with complete recovery between Sometimes associated hand/arm numbness, no other consistent symptoms This episode concerning due to ‘stabbing’ mid-frontal headache with photo/phonophobia, left arm and leg weakness, and lasted over 2 hours. Onset while out in the heat gardening. ROS: fatigue, chest discomfort, neck pain

4. PMHx/SurgHx COPD Hyperlipidemia Depression Septic thrombophlebitis, R Cephalic vein Appendectomy Hemorrhoidectomy

5. Family History Mother: Bell’s Palsy, Thyroid disease Father: Meniere’s Disease Grandmother: Stroke

6. Soc Hx Married, lives locally Diesel mechanic Smokes 1ppd x 30 years No use of EtOH or Recreational Drugs

7. Medications Verapamil 60mg TID Carbamazepine 200mg BID Aspirin 325 qD Famotidine 10mg qD Trandolapril 2mg qD Multivitamin Simvastatin 40mg qHS Albuterol PRN Allergy: Minocycline

8. VS: 132/80 36.6 p67 r18 GEN: alert, cooperative, pleasant, NAD. CV, Pulm, MSK examinations normal MS: oriented to person/place/time/situation Speech: slight labial dysarthria. Language normal. CN: NLF flattened on the right, decreased pinprick Right V1-3*

9. Motor: Tone and bulk normal, 5/5 throughout Sensory: decreased pinprick Right UE & LE Reflexes : Coordination: normal F-N-F and Heel-shin Gait: normal x4, no Romberg 2 2 22 22 1 3 1 ~~ 3

10. ?

11. Workup (occurred over ~1 year) Imaging: – MRI of complete neuro-axis: normal – CTA head and neck: normal – Trans-esophageal Echocardiogram: normal – 4-vessel angiogram normal Prolonged and Video EEG negative for epileptic event, no slowing, no change on trial of Keppra PET: Left lower lobe infiltrate likely pneumonia, no neoplasm

12. Lumbar Punctures: RBCsWBCsProtGlu Presentation 9020 (88%L) 6249 2 days later 275015 (51%L) 8059 7 days later 14010 (77%L) 8360 1 month later 12 7060 7 months later 12 5163 13 months later 55033 (94%L) 7660

13. No growth of bacteria or fungus Cryptococcal Ab: negative Oligoclonal bands: negative IgG index 0.59 ACE: <4 Cytology: negative x4 Extensive workup with ID: unremarkable Autoimmune/paraneoplastic workup: normal DRVVT + on 3 months after presentation but normal on subsequent 6 months later: “possible transient due to viral infection” EBV studies: +Capsid IgG +Nuclear ag ab +Early ag ab; - Capsid IgM

14. ??

15. Mollaret’s Meningitis v. Pseudomigraine with Temporary Neurologic Symptoms and Lymphocytic Pleocytosis started empiric treatment with Acyclovir IV, then Valacyclovir 1000mg daily x 1 year Increased verapamil for continued possibility of vasospasm

16. Mollaret, P. Revue Neurologique. 1944. Shalabi, M. Clinical Infectious Diseases. 2006. Mollaret’s Meningitis Described in 1944 >3 episodes of fever and meningismus; weeks to years between Lasting 2-5 days, wide variation Spontaneous resolution ~50% with neurologic features Pierre Mollaret (1898-1987)

17. Most commonly due to HSV-2, often with muco- cutaneous lesions found elsewhere Diagnosis confirmed with CSF HSV PCR Valacyclovir prevented genital lesion recurrence in first year, but no change in meningitis frequency Canadian Medical Assn. http://www.cmaj.ca/content/174/12/1710.2/F2.expansion.htmlhttp://www.cmaj.ca/content/174/12/1710.2/F2.expansion.html Ginsberg L. Pract Neurol 2008;8:348-361 Aurelius E. Clinical Infectious Diseases.2012.

18. Pseudomigraine with Temporary Neurologic Symptoms and Lymphocytic Pleocytosis = Migrainous Syndrome with CSF Pleocytosis = Syndrome of Transient Headache and Neurologic Deficits with CSF Pleocytosis (HaNDL)

19. HaNDL First described in 1981 Self-limited, benign condition Transient neurological deficits - 15 minutes to 2 hours each, over weeks-months Moderate-Severe throbbing headache Lymphocyte predominant pleocytosis – Avg 199 cells (range 10-760), most >90% Lymph; – avg protein 96, elevated in 96% – Glucose normal – Opening pressure elevated in ~50% Bartleson, JD. Neurology. 1981 Gomez-Aranda, F. Brain. 1997

20. Usually in 30s-40s (range 7-52 yrs) 25-40% had preceding cough/rhinitis/fatigue/diarrhea No consistent gender predominance

21. Neuroimaging is usually normal – Leptomeningeal enhancement – Hypoperfusion on CT perfusion EEG generally shows slowing in the corresponding region Other Studies

22. HaNDL Etiology Inflammatory/Infectious? – Few reports; Echovirus, HHV-6. Migrainous? – SPECT imaging with decreased blood flow at sites corresponding to neurologic deficit – spreading cortical depression phenomenon Infectious, triggering cortical depression? Castels-van Daele, M. Lancet. 1981. Emond, H. Cephalalgia. 2009. Caminero, AB. Headache. 1997

23. Diagnosis / Tx Must first exclude more sinister causes CSF with >15 cells/mL of lymphocyte predominance Episodes of moderate-severe headache occurring with or shortly following symptoms Episodes recurring within 3 months Symptomatic treatment only, if needed The International Classification of Headache Disorders: Cephalalgia. 2004

24. Our Patient frequency of attacks 3-4 per day (from up to 20). Mostly affecting only his right face Usually associated with moderate headache Happy with improvement

25. Shalabi M, Whitley RJ. Recurrent benign lymphocytic meningitis. Clinical Infect Dis. 2006;43(9):1194. L Ginsberg, J Kidd. Chronic and Recurrent Meningitis. Pract Neurol 2008;8:348-361. Aurelius E, Franzen-Röhl E, Glimåker M. Long-term valacyclovir suppressive treatment after herpes simplex virus type 2 meningitis. Clin Infect Dis. 2012;54(9):1304. Bartleson JD, Swanson JW, Whisnant JP. A migrainous syndrome with cerebrospinal fluid pleocytosis. Neurology. 1981;31(10):1257. Castels-van Daele M, Standaert L, Boel M, Smeets E, Colaert J, Desmyter J. Basilar migraine and viral meningitis. Lancet. 1981;1(8234):1366. Caminero AB, Pareja JA, Arpa J, Vivancos F, Palomo F, Coya J. Migrainous syndrome with CSF pleocytosis. SPECT findings. Headache. 1997;37(8):511. Gómez-Aranda F, Cañadillas F, Martí-MassóJF. Pseudomigraine with temporary neurological symptoms and lymphocytic pleocytosis. A report of 50 cases. Brain. 1997;120 ( Pt 7):1105.