Differential diagnosis of thunderclap headache

Subarachnoid hemorrhage
unruptured aneurysm
cerebral sinus thrombosis
cervical artery dissection
hypertensive crisis
spontaneous intracranial hypotension
acute ischemic stroke
acute cerebral hematoma
pituitary apoplexy
intracranial infection
"benign" thunderclap (explode category)

Treatable autoimmune encephalitis

Bataller L et al. Autoimmune limbic encephalitis in 39 patients: immunophenotypes and outcomes. JNNP 2007: 78: 381-385.

17 patients were studied at University of Pennsylvania, as well as 22 "outside cases" with sera sent in. . The most important points were that

1. Most of the patients were accurately diagnosed clinically before antibodies were returned.

2. 9/17 had antibodies to known neuronal antigens (paraneoplastic or VGKC's) and 5/17 to novel cell membrane antigens (hippocampus/cerebellum). For the whole group, including the sent in cases, the numbers were 19/39 had antibodies to known antigens, 17/39 to nCMA's.

3. A significant treatment response effect was seen in those with VGKCA's and nCMA's.

4. Those with known intraneuronal antigens (anti Hu, anti Ma) are associated with cancer and may be associated with a worse prognosis than the antibodies to VGKCA's and nCMA's

5. Ovarian teratoma and thymoma are paraneoplastic treatable and benign conditions once the tumor is excised

6. No MRI or CSF characteristics help in diagnostic process.

In another article, some cases of ovarian teratoma associated paraneoplastic encephalitis are related to NMDA receptor antibodies (NMDAR) (Dalmau J, et al. Ann Neurol 2007; 61: 25-36. ) Posner's group described 12/12 with teratomas of ovary who had NMDAR with antibodies to the NR2 subunit, which binds glutamate in the forebrain and hippocampus, AND, a VIRUS LIKE PRODROME.

In yet another article, Mathew et al. (Neurology 2007; 68: 900-905) described orchiectomy for Ma2 related encephalitis as successful in showing otherwise undocumented tumors in 6/25 patients who underwent the procedure (the other 19 had known germ cell tumors). The criteria for orchiectomy were 1) present Ma2 antibodies with clinical/MRI evidence of encephalitis 2) life threatening or progressive neurologic deficits 3) age< 50 4) absent evidence for other tumors 5) new testicular enlargement, microcalcifications on testicular ultrasound, cryptorchidism or other evidence of testicular disease. All testicular specimens showed germ cell tumors. Tumor markers, body CT, PET, and other tests were negative in those undergoing the procedure.

Other antibodies reported include Hu, Ri, Ma1, Ma2, CAR, CRMP 3, amphiphysin, and others.

Thunderclap headache and benign CNS angiopathy

Chen SP et al. Reccurrent primary thunderclap headache and benign CNS angiopathy: spectra of the same disorder? Neurology 2006; 67:2164-2169.

56 patients with recurrent thunderclap headache were recruited. Segmental vasoconstriction was found in 22 (39 %). HA recurred .7 times per day for fourteen days. Each attack lasted 3 hours, and 84 % of patients reported at least one trigger. Nimodipine aborted attacks in 83 % and stopped headaches within 3 months. 4 patients (7%) developed stroke. Authors note that this entity is identical to benign CNS angiopathy. Exertion and defecation are greater triggers in vasoconstriction group.  Other triggers are emotional situations,laughing, bathing, bending down.

Blogger note: this is identical to Call Fleming syndrome frequently discussed in USA. See http://strokenotes.blogspot.com/search?q=call for more minutiae about it.

Review article
Ducros A. Reversible cerebral vasoconstriction syndrome.  Lancet Neurology 2012;11:906-917

additional pearls

1.  Pain peaks in 1-2 weaks, angiogram findings in about 3 weeks.

2.  Many synonyms exist (see below)

3.  Thunderclap headache usually peaks within 1 minute, unilateral or bilateral and mimics aneurysm rupture; each episode may last 3 hours but can vary with up to 3 day duration, and 4 attacks over the 3 month period with moderate headache in between

4.  Ten percent have focal findings; ten percent may have seizures including inaugural, and they rarely recur.  Marching numbness can mimic migraine, focality, a stroke.

5. Beware of neck pain (dissection).  Other differentials are CVT (check d Dimer and MRV), transfusion or products (red cell transfusion, alpha interferon, IVIG), phenytoin intoxication, CEA, low pressure headache.

6.  May screen for pheochromocytoma or glomus tumor or carcinoid. Do a drug screen in some patients.  Not only is cocaine in differential, cannabis is a trigger as well as LSD.  Other triggers include SSRI's, triptans, ergot derivatives, nicotine patches, ginseng and binge drinking.  Inquire about scorpion poison and star fruit.

7.  Convexity SAH may be subtle, and missed on CT, strokes occur in watershed areas (including cerebellar watershed areas); brain edema can mimic PRES.

8.  Catheter angiography can trigger TIA. 

9. Postpartum cases occurs in first week after delivery.  Inquire about exposure to vasoconstrictors during anesthesia, depression. 

10.  Synonyms and old names:  isolated benign CNS vasculitis, acute benign cerebral angiopathy, reversible cerebral segmental vasoconstriction, Call Fleming syndrome, CNS pseudovasculitis, benign angiopathy of CNS, postpartum angiopathy, migraine angiopathy, migraine angiitis, migraine vasospasm, primary thunderclap headache, cerebral vasculopathy, vasospasm infatal migrainous infarction

11.  Factors that independently make RCVS worse:  those who receive glucocorticoids, serotonergic antidepressants, patients with ischemic stroke (Singhal AB, Topcuoglu MA. Glucocorticoid associated worsening in reversible cerebral vasoconstriction syndrome.  Neurology 2017; 88:228-236.

Transient epileptic amnesia syndrome

Butler CR, Ann Neurol 2007; 61:587-598

Another hard to diagnose syndrome. 50 patients were recruited with recurrent amnesia, other cognitive functions intact, and compelling evidence of epilepsy. 24 controls also were studied. Clinical pearls to diagnosing this include: average age 62, frequent spells (eg one a month for a year), duration 30-60 minutes, occurrence upon awakening, prompt cessation with antiepileptic drug treatment. Neurocognitively patients complained of forgetting, but did well on standard (? what) neuropsych, but with accelerated forgetting of verbal and visual material over 3 weeks and some loss of autobiographical memory. Its diagnosis is usually missed.

Ictal asystole: clinical characteristics & SUDEP

Neurology 2007; 69: 434-441.


Occurred in .27 % of patients undergoing VEEG. There was a sudden loss of atonia 42 seconds into the seizure with characteristic EEG findings of hypoperfusion. It occurred in TLE and extratemporal epilepsy. Clinical predisposing characteristics were not identified. Patients should be sent for pacemakers to avoid SUDEP.

Other predisposing factors for SUDEP are long QT syndrome, Brugada syndrome, and catecholaminergic ventricular arrythmia. Absence of treatment or insufficient treatment are neurologic risk factors. 

Carbamazepine, which can decrease heart rate variability, has been proposed as a risk factor for SUDEP.  SUDEP in most cases is triggered by a GTCS.  Four cases that were monitored during SUDEP showed EEG flattening before cardiorespiratory changes.  Another showed seizure triggered ventricular fibrillation.  Sleeping prone may be a risk factor,

Nice review article:
Tomson T, Nashef L, Ryvlin P.  Sudden unexpected death in epilepsy:  current knowledge and future directions.  Lancet Neurology 2008; 7:1021-1031.

More pearls  Kloster R. et al. JNNP 1999; 67:439-444

risk factors
male  predominance
Laying prone (17/24) usually during sleep.
At least one AED is subtherapeutic
Pulmonary edema is present in 26/42
Seizure just before death in 28/39

Alcohol levels were usually zero.

NeuroBehcet's pearls

multiple sources but NEJM CPC from May 28, 2009 was one.

1. Known as Silk Route disease due to occurrence along trading paths in Asia
2. Criteria include (major) oral ulcers occurring at least three times per year, genital ulcers or scars, ocular involvement (uveitis), skin (erythema nodosa, folliculitis, acne), positive skin pathergy test. Minor criteria are arthritis, DVT, superficial thrombophlebitis, epididymitis, positive family history, GI, CNS, or vascular involvement.
3. Neurologic involvement occurs in 5-10 %, with vascular involvement (venous sinus thrombosis or arterial thrombosis), or parenchymal infiltration. Brain stem and basal ganglia are common areas of predilection. The disease can be relapsing-remitting, chronic progressive, or secondary progressive.
4. Abnormal labs include high sed rate, CRP, complement, IL6,8 , TNF, and distinctive CSF neutrophilic pleocytosis.
5. Best treatment is not know, but in CPC authors suggested high dose pulsed steroid and cyclophosphamide, and maintenance immunoosuppression with azathioprine.

GAD 65 autoimmunity in PSP mimics

Article with reply by Mayo group in Neurology 1009 June. Original case was a 54 year old woman with supranuclear gaze plasy and parkinsonism mimicking PSP. There were stiff man like symptoms and strong GAD65 positivity. PSP was excluded in part by prominent early upgaze palsy, and startle induced spasms typical of SMS, and video ENG findings of a fatiguing pattern of saccade initiation with repetive saccades. The Mayo report (Pittock SJ, Mayo Clin Proc 2006) presented with brainstem, eps and spinal cord syndromes and were initially misdiagnosed as PSP or MSA. Pittock's group also reported OCB in CSF and improvement with prompt initiation of immunotherapy.

Superior division oculomotor paresis

Clin note in Neurology June 2009.

KEY POINTS
Clinical Patient has diplopia in vertical gaze, right ptosis, and right retroorbital pain. Exam showed ptosis, hypotropia, and elevation paresis in the right eye (looking in and up). Angio showed cavernous right ICA aneurysm that was coiled. The IIIn divides into superior and inferior divisions near SOF or anterior cavernous sinus. Clinical presentation is ptosis and superior rectus palsy.