Lymphocytic hypophysitis – 10/3/18

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!


Clinical Pearls

  • 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
  • Fever
  • Focal neurologic findings
  • New headache in immunosuppressed patient

Pituitary adenoma:

  • 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
    • Hyposecretion:

Capture

Hypophysitis:

  • Inflammation of the pituitary
  • Four categories based on histologic findings:
    • Lymphocytic
      • Most common form
      • Seen in late pregnancy and post-partum period
      • Also associated with ipilimumab as our patient here!
    • Granulomatous
      • 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
  • Prognosis:
    • Pituitary size eventually normalizes but pituitary loss of function is often permanent.

Hyponatremia:

Lastly, refer to this algorithm from our recent morning report to help you think through hyponatremia.

Wound botulism – 9/26/18

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.


Clinical Pearls

  • 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)

Capture

For more information, check this prior post on our blog.

Ophthalmoplegic migraine – 9/25/18

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.


Clinical Pearls:

  • 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:

Capture

Ophthalmoplegic migraine:

  • 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)

 

 

Mute and Unresponsive… 8/29/2018

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!

Catatonia

  • Features:
    • Hypokinesis or akinesis
    • Excessive purposeless movements
    • Mutism
    • Decreased alertness/response to stimuli
    • Negativism (resistant to all instructions, commands)
    • Posturing
    • Fixed stare
    • Echolalia (repetition of another person’s words) or echopraxia (repetition of another’s actions)
    • Subtypes
      • 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
      • Management:
        • 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.

NMS

  • Tetrad:
    • Encephalopathy
    • Muscular rigidity (lead pipe)
    • Hyperthermia
    • 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 vs Catatonia

NMS can be a spectrum:

Woodbury

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:

NMS SS

 

Encephalitis and CJD! – 8/22/18

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).


Clinical Pearls

  • 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!

Encephalitis:

Defined as AMS > 24 hours plus 2 of the following:

  1. Fever
  2. Focal neurologic deficit
  3. Seizure
  4. CSF pleocytosis
  5. Abnormal findings on EEG or neuroimaging

Differential

Capture

Prion diseases:

  • 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

CJD: 

  • 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)

Diagnosis:

  • 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)

Prognosis:

  • Poor, majority die within 1 year
  • No treatment available

Paradoxical stroke in patient with ASD – 7/9/18

Today, Joe presented the case of a young woman presenting with acute onset of L sided weakness, found to have a paradoxical stroke due to ASD!


Clinical Pearls

  • Paradoxical stroke is a diagnosis of exclusion
  • Atrial septal defects (ASDs) have been associated with cryptogenic stroke (stroke of unknown etiology).  An embolic source is often not identified.
  • Ostium secundum is the most common type of ASD (>70% of cases)
  • Indications for ASD closure include the following
    • Symptomatic patient (DOE, platypnea-orthodeoxia)
    • R sided cardiac chamber enlargement
    • Left to right shunt >1.7:1
    • Before pacemaker or device placement
    • After a stroke
  • What about PFOs and cryptogenic stroke?
    • In the past, the recommendation was not to close them.  However, the 2017 CLOSE and REDUCE trials (as well as the 2013 RESPECT trial) showed that closure of PFO reduces the risk of a second stroke compared with medical therapy alone.  Thus, the latest ACC recommendation is to close PFOs after stroke!

Etiologies of stroke in a young adult:

  1. Hypercoagulable state
    • Inherited disorders
      • Protein C/S deficiency
      • Factor V Leiden
      • Prothrombin 20210 mutation
      • High homocysteine levels
      • Sickle Cell Disease
    • Acquired disorders
      • Pregnancy
      • OCPs
      • Estrogen hormone replacement therapy
      • Malignancy
      • APLS
      • DIC
  2. Vasculopathy
    • Noninflammatory
      • Dissection
      • Trauma
      • Connective Tissue Disease
      • Fibromuscular dysplasia
      • Migraine with aura
    • Inflammatory
      • Vasculitis
        • Large vessel: Takayasu, GCA
        • Small to medium: Kawasaki, PAN
      • Secondary vasculitis
        • Bacterial meningitis
        • HIV
        • Varicella
        • Syphilis
        • TB
        • Fungi (esp cocci)
    • Malformations
      • AVMs –> hemorrhagic
      • Aneurysms –> hemorrhagic
    • Venous
      • Cerebral venous sinus thrombosis
    • Other
      • Moyamoya
  3. Metabolic
    • Vessel injury
      • CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)
      • Fabry
      • Homocystinuria
    • Pure metabolic
      • MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes)
      • Organic acid disorders
  4. Drugs
    • Cocaine
    • Meth
  5. Cardiac
    • Congenital
    • Rheumatic valve disease
    • Mitral Valve Prolapse
    • PFO
    • ASD
    • Endocarditis with septic emboli
    • Atrial myxomas
    • Fibroelastoma
    • Arrhythmias
    • Cardiac surgery

Atrial Septal Defects

  • Secundum is seen in 75% of cases
  • Exam findings:
    • Fixed split S2
    • Parasternal impulse
    • Mid-systolic mumur at LSB (can be mid-diastolic also)
    • EKG with RV strain and partial RBBB
  • Indications for closure:
    • After stroke
    • Symptomatic patient
      • DOE
      • Platypnea-orthodeoxia syndrome
    • R sided cardiac chamber enlargement
    • L to R shunt > 1.7:1 (based on TTE findings)
    • Before pacemaker/device placement

 

Subacute combined degeneration of spinal cord – 7/3/18

Brooke presented a fascinating case of a middle aged man with history of substance use disorder presenting with acute on chronic back pain, weakness, and urinary retention, found to have subacute combined degeneration of the spinal cord from vitamin B12 deficiency due to using >100 canisters of nitrous oxide daily!


Clinical Pearls

  • Vitamin B12 deficiency can lead to degeneration of the dorsal and lateral white matter of the spinal cord ⇒ subacute combined progressive weakness, sensory ataxia, paresthesias, spasticity, paraplegia, and incontinence.
  • Nitrous oxide use (“Whippits”) inactivates vitamin B12 in the blood, rendering the body effectively vitamin B12 deficient.
    • In patients with history of N2O abuse, always check MMA levels with vitamin B12 since the latter is not a marker of functional B12 availability.
    • Treatment involves high dose B12 supplementation and stopping Whippits!

Differential for myelopathies:

  • Syringomyelia ⇒ cavitation of central spinal cord resulting in LMN symptoms with sensory changes
  • Inflammatory
    • Transverse myelitis
      • Viral prodrome
      • Usually associated with MS or autoimmune diseases
      • Typically involves the thoracic cord
      • Symptoms develop over hours
    • Sarcoid
      • Mimics transverse myelitis or tumor
    • Praneoplastic syndromes
  • Infectious
    • Epidural abscess
    • Acute viral myelitis
      • Enteroviruses (coxsackie, polio), flaviviruses (WNV, Japaneses encephalitis)
      • CMV, VZV, HSV, HCV, EBV (these viruses are less clearly associated)
    • AIDS myelopathy
    • HTLV-1 myelopathy
    • Syphilis
      • Tabes dorsalis (affects dorsal columns)
    • TB
    • Parasites
      • Schistosoma, cysticercosis
  • Vascular
    • Spinal cord infarction
    • Vascular malformations
    • Spinal epidural hematoma
  • Toxic/metabolic disorders
    • Subacute combined degeneration of spinal cord ⇒ degeneration of dorsal and lateral white matter (think Whippits and B12 deficiency!)
    • Copper deficiency myeloneuropathy
    • Radiation induced myelopathy
    • Hepatic myelopathy (purely motor symptoms, lower extremities predominant, in patients with ESLD)
    • Decompression sickness myelopathy (in deep sea divers)
  • Neoplasms
  • Degenerative conditions
    • ALS
  • Demyelinating diseases
    • MS

Inhalant Abuse:

Side effects are broad and include

  • CNS effects
  • CV: arrhythmias, myocarditis, MI “sudden sniffing death”
  • Pulmonary: hypoxia, pneumonitis, hemorrhagic pulmonary edema, PTX from pressurized tanks
  • GI: n/v, abdominal cramps, anorexia, hepatotoxicity
  • Renal effects: AGMA (with volatile substances), urinary calculi, nephrolithiasis
  • Hematologic: aplastic anemia, malignancy (leukemia, lymphoma, MM)
  • Derm: “Glue-sniffer’s rash”. Eczematoid dermatitis with erythema, inflammatory changes, and pruritis in the perioral area and midface
  • MSK: rhabdo