Thanks to Katie for presenting the interesting case of a young man with history of disseminated TB with TB meningitis and hydrocephalus requiring VP shunts, admitted for acute LUE weakness, L homonymous hemianopsia, and memory impairment, found to have acute strokes in multiple vascular territories due to TB related CNS vasculitis!
- Remember that arterial dissection is the most common cause of stroke in a young patient.
- CNS vasculitis can be primary or secondary to a systemic illness. It typically presents with infarcts in multiple vascular territories. Treatment involves immunosuppression with high dose steroids + cytoxan/rituxan.
- CNS vasculitis is the most common cause of severe neurologic deficit in patients with TB meningitis.
- Vasculitis in CNS TB is the result of a hypersensitivity reaction to proteins released from the bacteria.
- TB meningitis requires an extended course of anti-TB treatment, generally up to 1 year or more. Serial LPs are obtained to monitor adequate response to therapy.
Etiologies of stroke in a young adult
- Coagulopathy (think of conditions that cause both arterial and venous thrombosis)
- Hyperviscosity states
- Leukostasis in setting of leukemia
- Sickle cell
- Myeloproliferative disorders (PV, ET, CML)
- Paroxysmal nocturnal hemoglobinuria
- Dissection (most common cause of stroke in a young person)
- Malformations (AVMs, aneurysms, moyamoya)
- Cerebral venous sinus thrombosis
- Primary vasculitis
- Large vessel: Takayasu, GCS
- Small to medium: Kawasaki, PAN, ANCA-associated
- Secondary vasculitis
- Bacterial meningitis
- Fungi (esp cocci)
- Collagen vascular disease (i.e. lupus)
- CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)
- Organic acid disorders
- Rheumatic valve disease
- Mitral valve prolapse
- Endocarditis with septic emboli
- Atrial myxoma
- Cardiac surgery
Three main manifestations:
- TB meningitis (most common presentation in low incidence settings like the US)
- Intracranial tuberculoma
- Spinal tuberculous arachnoiditis
Spillage of tubercular protein into the subarachnoid space results in an intense hypersensitivity reaction and inflammation resulting in
- Proliferative arachnoiditis (fibrous mass encasing cranial nerves and vessels adjacent to it)
- Vasculitis with resultant aneurysm, thrombosis, and infarction
- Communicating hydrocephalus
- 1% of all TB cases, 5% of all extrapulmonary TB cases
- 15-40% mortality rate
- Clinical manifestations
- 3 stages:
- Prodromal phase: malaise, headache, low grade fever, personality changes
- Meningitic phase: meningismus, headache, vomiting, lethargy, confusion, CNS signs, some motor deficits
- Paralytic phase: stupor, coma, seizures, hemiparesis (death within 5-8 weeks)
- Characteristic CSF findings of low glucose, elevated protein, lymphocytic pleocytosis
- CSF AFB smear and culture: in general, a minimum of 3 serial LPs should be performed, as diagnostic yield increases f
- Nucleic acid tests: Xpert MTB/RIF assay should be submitted in the setting of high clinical suspicion and negative AFB staining.
- Intensive phase (2 months): four drugs RIPE. Ethambutol has poor CNS penetration so some use fluoroquinolones instead.
- Continuation phase (7-10 months)
- A review of 9 trials on 1337 patients found that use of steroids reduced death and disability by ~25%.
- Benefit higher if started earlier in disease process.
- Treat for 8 weeks, slow taper.
- A retrospective study in Stroke 2018 on patients with TB meningitis found that those >40, with concurrent HTN, dysplipidemia, and DM were more likely to have this complication. Some small case series showing benefit in reducing future strokes with the use of Aspirin.
- No role for tPA.
Thanks to Arathi for presenting the case of a middle-aged man with poorly controlled diabetes who presented with blurry vision and ear pain, found to have multiple cranial nerve palsies, diagnosed with skull base osteo, septic dural sinus thrombosis, and orbital cellulitis!
- Septic thrombophlebitis is venous thrombosis with inflammation in the setting of bacteremia and can impact any vein. Most common cause of this condition in the hospitalized patient is indwelling lines and catheters.
- Septic thrombophlebitis of the jugular vein is called Lemierre’s syndrome and is frequently preceded by pharyngitis.
- Septic dural sinus thrombosis is extremely rare (only several hundred cases diagnosed in recent history). The most common presenting symptom is headache. There are three types:
- Cavernous sinus thrombosis
- Lateral (transverse) sinus thrombosis (rare)
- Superior sagittal sinus thrombosis (very rare)
- Cavernous sinus thrombosis can present with CN III, IV, V1, V2, VI palsies. Of these, CN VI is the first one to get affected. So for patients presenting with lateral gaze palsy and headache, think cavernous sinus thrombosis!
- The mainstay of treatment for septic dural sinus thrombosis is antibiotics. Most common organism involved is staph aureus.
- The role of anticoagulation is controversial. The few retrospective studies done have shown a potential reduction in mortality/morbidity without a significant increase in risk of ICH. Common practice currently is to start anticoagulation with heparin early on especially in patients with unilateral symptoms.
Septic dural sinus thrombosis
- Uncommon disease with only several hundred cases reported in the antibiotic era. So you might only see one in your whole career!
- Difficult to diagnose and often diagnosis and treatment are delayed.
- Encompasses three basic syndromes: manifestations of each are unique
- Cavernous sinus thrombosis
- Lateral sinus thrombosis
- Superior sagittal sinus thrombosis
- All three manifest as severe headaches which are often the presenting symptom.
Septic cavernous sinus thrombosis
- Most common. Lots of trabeculae to trap bacteria.
- Clinical manifestations
- Headache and cranial nerve palsies should raise your suspicion!
- Fever, periorbital edema. Pain is usually unilateral, retroorbital and frontal in nature with radiation to the occiput.
- Altered mental status especially in older people
- Less common: photophobia, tearing, and ptosis
- B/l ptosis, proptosis, chemosis, and ocular muscle paralysis but can be subtle
- Fundoscopic exam with papilledema
- Lateral gaze palsy (isolated CN VI) is the first manifestation because of the location of the nerve in the cavernous sinus.
- Loss of visual acuity from papilledema
- Compression of optic nerve by mycotic aneurysm of the intercavernous segment of the internal carotid/ophthalmic artery can lead to blindness.
- CSF can show inflammatory cells in 75% of cases.
- Staph aureus is the most common (70%) followed by strep and anaerobes.
- CT venogram or MR venogram
- Antibiotics: IV and prolonged for at least 3 weeks b/c thrombus may prevent abx penetration
- Anticoagulation: No prospective data. One retrospective study showed a significant reduction in mortality in patients with unilateral involvement who presented early and received heparin. A second showed no change in mortality but decreased morbidity. No increased risk of ICH. Based on these small studies, experts suggest heparin early on in patients with unilateral CST. Duration of anticoagulation is at the discretion of the clinician (no data).
- Surgery: Drainage of sinus infection if present, otherwise no benefit.
- No role for steroids
- Mortality is 30%
- Infection can spread to meninges and the pituitary and morbidity can reach 50%.
- 30% suffer serious sequelae:
- Persistent oculomotor weakness
- Pituitary insufficiency
Septic lateral sinus thrombosis
- Rare due to early treatment of otitis media. Generally results from untreated OM à mastoiditis à lateral sinus thrombosis.
- Earache is generally the first symptom for several weeks
Septic superior sagittal sinus thrombosis
- Extremely rare
- Usually due to bacterial meningitis
- Complete thrombosis is universally fatal.
Differential for cavernous sinus obstruction:
- septic thrombosis
- intra-orbital abscess
- Tolosa-Hunt syndrome (granulomatous inflammation of the superior orbital vein and cavernous sinus)
- Polyarteritis nodosa (Cogan syndrome)
- IgG4 dz
- Nasopharyngeal tumor
Skull base osteomyelitis:
- Frequently seen in elderly patients with poorly controlled diabetes or immunocompromise
- Most commonly a complication of malignant otitis externa.
- Results in multiple cranial nerve palsies VII through XII due to involvement of the stylomastoid, jugular, and hypoglossal foramens.
- Treatment requires antibiotics for at least 4-6 weeks.
Thanks to Sahar for presenting the interesting case of a middle-aged woman with metastatic melanoma recently started on ipilimumab who presented with a headache and fatigue, found to have hypothyroidism and adrenal insufficiency with work up consistent with hypopituitarism related to an adverse effect of ipilimumab: lymphocytic hypophysitis!
- Remember that adrenal insufficiency and hypothyroidism are causes of elevated ADH levels.
- Red flags for obtaining head imaging for headache include age >55, sudden onset, positional, onset after trauma or exercise, fever, focal neuro findings, and immunosuppression.
- Pituitary adenomas can have three manifestations: mass effect, hormonal hypersecretion, and hypopituitarism. When imaging shows a pituitary mass, your work up should address each of these categories.
- The most sensitive test to assess hypothalamic-pituitary access function is LH/FSH!
- Immunotherapies are commonly associated with a flare of autoimmune diseases. A more rare side effect of CTLA-4 inhibitors (like ipilimumab) is lymphocytic hypophysitis (inflammation of the pituitary gland)
- This condition commonly presents with headache out of proportion to neurologic findings and preferential decline in ACTH and TSH though other hormones can also be impacted.
- For hypopituitarism, remember to always treat adrenal insufficiency first before replacing thyroid hormone. Failure to do so can precipitate adrenal crisis!
Indications for imaging a patient with headache:
- Age >55
- Sudden onset
- Worse with lying down or wakes patient from sleep
- Rapid onset after trauma or exercise
- Focal neurologic findings
- New headache in immunosuppressed patient
- Evaluate for the following
- Mass effect: visual field deficit, headache
- Hormonal hypersecretion
- Prolactin ⇒ galactorrhea, amenorrhea, infertility
- GH ⇒ Acromegaly
- TSH ⇒ hyperthyroidism
- ACTH ⇒ Cushing disease
- ADH ⇒ SIADH
- Inflammation of the pituitary
- Four categories based on histologic findings:
- Most common form
- Seen in late pregnancy and post-partum period
- Also associated with ipilimumab as our patient here!
- Idiopathic or secondary to GPA, sarcoid, TB
- Plasmacytic (IgG4-related)
- Xanthomatous (most rare)
- Clinical presentation
- Headache out of proportion to exam findings
- Preferential decrease in ACTH and TSH ⇒ adrenal insufficiency and hypothyroidism
- Pituitary size eventually normalizes but pituitary loss of function is often permanent.
Lastly, refer to this algorithm from our recent morning report to help you think through hyponatremia.
Thanks to Alison for presenting the case of a middle aged man who presented with acute onset of ptosis, dysphagia, and dysarthria, with an evolving exam found to have botulism secondary to IV injection of black tar heroin.
- Botulism is extremely rare! Only 110 cases were reported last year in the US with 70-75% of them being related to infant botulism, 20-25% foodborne, and 5-10% wound botulism. The latter category has been on the rise especially in California.
- Most common form of botulism is infant botulism
- Botulism presents with bulbar symptoms; progressive, descending paralysis; absent reflexes; and autonomic dysfunction
- Management involves the following
- Notify the Department of Public Health ASAP if botulism is on your ddx
- Obtain wound/blood cultures (special tube to be sent to DPH)
- Administer antitoxin EARLY (do NOT wait for culture confirmation)
For more information, check this prior post on our blog.
Thanks to Joe fore presenting the case of a middle aged woman with a history of migraines who presented with acute onset of painless binocular diplopia, found to have an isolated CN3 palsy concerning for ophthalmoplegic migraine after an extensive work up.
- Types of diplopia:
- Binocular diplopia refers to diplopia that is only present when both eyes are open (goes away when one eye is closed) and results from ocular misalignment.
- Monocular diplopia refers to diplopia that is present even when one eye is closed and is more consistent with a local eye disease (globe related processes involving the cornea or the lens).
- Approach to diplopia is similar to any neurologic deficit in which you would localize the lesion!
- Upper motor neuron (brain)
- Peripheral nerve (cranial nerves)
- Neuromuscular junction
- Muscle (extra-ocular muscles)
- Globe (local eye disease or refractive error)
- CN3 palsy usually presents with the eye in the “down and out” position and can also impact the levator palpebrae muscle resulting in ptosis. These result from ischemia at the center of the nerve (secondary to diabetes/HTN).
- In a patient with CN3 and a dilated pupil, you must rule out a PCA aneurysm! Impingement of the CN3 by an enlarging aneurysm cuts off the parasympathetic fibers running on the outside of the nerve, resulting in a dilated pupil. This is the only aneurysm that gives a warning sign before rupture!
Commonly tested gaze palsies:
- Rare condition, often manifests in children and young adults
- Diagnosis of exclusion
- Most commonly affects CN3 (but can go to CN4 and CN6 as well)
- Can sometimes precede the headache
- Permanent nerve damage has been reported and some believe that it is a demyelinating neuropathy (for more info, refer to this review article)
Today Elise presented a case of a middle age woman, with a history of schizoaffective disorder and recent psych med changes, who came in unresponsive and mute. She was hypertensive and catatonic on exam but afebrile. Labs revealed moderately elevated CK. She responded well to IV Ativan. The final diagnosis was drug-induced catatonia!
- Hypokinesis or akinesis
- Excessive purposeless movements
- Decreased alertness/response to stimuli
- Negativism (resistant to all instructions, commands)
- Fixed stare
- Echolalia (repetition of another person’s words) or echopraxia (repetition of another’s actions)
- Retarded Catatonia:
- Mainly negativism, hypokinesis, mutism, staring.
- +/- anorexia, incontinence, stupor
- Excited catatonia:
- Hyperkinesis, restlessness, impulsivity, aggression
- Malignant catatonia
- Life threatening: Fever, autonomic instability (labile BP, tachycardia, tachypnea, diaphoresis), delirium, rigidity.
- Labs: Leukocytosis, elevated CK
- Thought to be a spectrum of NMS
- Withdrawal of offending medication if suspecting drug-related
- Initial treatment: Benzos, if pt improves with the “benzo challenge,” then this supports the dx of catatonia.
- Electro-convulsive therapy is an option.
- Muscular rigidity (lead pipe)
- Autonomic instability
- Associated with antipsychotics exposure, even some anti-emetics.
- Can present days to weeks after exposure.
- Management: DC offending agent, benzos, bromocriptine, supportive measures
NMS can be a spectrum:
NMS can be confused with Serotonin Syndrome! Key to get a detailed medication history since SS is due to Serotonin, and NMS is due to Dopamine pathways! There are certain clues on the exam and presentation that can distinguish the two:
Thanks to Joe for presenting the case of an elderly man presenting with subacute onset of AMS, vision changes, and ataxia, found to have creutzfeldt jakob disease (CJD).
- Rapidly progressive encephalitis should trigger prion disease, paraneoplastic encephalitis, or Whipple’s!
- Most common malignancies associated with paraneoplastic encephalitis are SCLC, testicular tumors, thymomas, breast cancer, and hodgkin lymphoma
- >90% of cases of CJD are sporadic
- Definitive diagnosis of CJD is made by brain biopsy. CSF testing of 14-3-3 protein marker and the RT-QuIC protein assay combined have sensitivity and specificity >90%.
- If prion diseases are on your differential, be sure to let infection control know before doing an LP because strict precautions are required to prevent spread of infection!
Defined as AMS > 24 hours plus 2 of the following:
- Focal neurologic deficit
- CSF pleocytosis
- Abnormal findings on EEG or neuroimaging
- AKA transmissible spongiform encephalopathies
- Rare, closely related, fatal, neurodegenerative conditions
- Occur in humans and mammals
- Result of accumulation of aggregated forms of the prion protein in the CNS
- >90% are sporadic, the rest are infectious (kuru, variant CJD, and iatrogenic CJD)
- Iatrogenic mostly resulting from receipt of growth hormone prepared from cadaveric pituitaries and contaminated cadaveric dura mater allografts
- Sporadic is not transmissible by blood
- Kuru was the first one recognized to be transmissible and linked to cannibalism among tribes in New Guinea
- Most prominent clinical feature is disordered cognition
- Typically, patients also have motor signs, such as ataxia or spasticity, vague sensory problems, or changes in visual perception
- Myoclonus is common
- Progressive neurologic decline resulting in death within 6-12 months
- One in a million
- Mean age of onset 57 – 62
- More common in white people (may be ascertainment bias)
- Elevated CSF levels of 14-3-3 are not very sensitive or specific. Adding RT-QuIC protein assay to the test increases both sensitivity and specificity to >90%.
- CDC requires the following criteria for diagnosis:
- Progressive dementia AND
- 2 of the following: myoclonus, visual or cerebellar disturbance, pyramidal/extrapyramidal dysfunction, akinetic mutism AND
- Atypical EEG and/or positive 14-3-3 CSF assay with clinical duration to death <2 years and or typical MRI abnormalities (see nice example here)
- Poor, majority die within 1 year
- No treatment available