Neuromuscular Disorders

This week in conference we covered a broad range of topics, from multiple sclerosis and Parkinson’s disease to TIA and stroke. As a review, lets focus on some of the key learning points of neuromuscular disorders.

The neuromuscular unit has four components: anterior horn cells in the spinal cord, the peripheral nerve, the neuromuscular junction, and the muscle innervated. The pathology based on what component is impacted determines the associated signs and symptoms (i.e. myelopathy – spinal cord, radiculopathy – nerve root as it exits the spinal cord, neuropathy – peripheral nerve, myopathy – muscle). Moreover, the location of the pathology leads to signs and symptoms that can help us locate the pathologic process and help with diagnosis:

Upper motor neuron involved (i.e. spinal cord) – increased deep tendon reflexes, muscle tone increased, positive Babinski/Hoffman’s signs, clonus

Lower motor neuron involved (ie. peripheral nerve) – decreased deep tendon reflexes, decreased muscle tone, muscle atrophy notable with chronicity, fasiculations may be present

When discussing presenting symptoms in patients with neuromuscular complaints, differentiate weakness from fatigue:

Weakness – inability to exert a normal force

Fatigue – decreased force with repetitive use

Also, as a focus of the physical examination, pay particular attention to the things we really care about in the ED, such as the patient’s ability to ventilate. Muscles used to lift the head off the bed may weaken before those of respiration and so should be assessed. Frequent measurements and reassessment of respiratory parameters such as forced vital capacity (FVC) and negative inspiratory force (NIF) should be used early and rechecked often if there is concern. Normal FVC is 60-70 mL/kg. When it approaches a reduction towards 15 mL/kg, ventilator support is likely necessary. Similarly, if the NIF is approaching a less negative value (i.e. -20 mmHg), this should raise alarm. Blood gasses are NOT helpful, as by the time the patient has developed hypercarbia or hypoxia from their neuromuscular weakness leading to ventilatory failure you’re too late.

On to a brief review of the main topics covered:

Myasthenia Gravis

Epidemiology: affects women 20-40 years old and men 50-70 years old typically.

Pathophysiology: autoantibodies to the nicotinic acetylcholine receptor (i.e. anti-ACh-R) or muscle specific tyrosine kinase leading to destruction of acetylcholine receptors with a decrease in the total number available and competition with acetylcholine for binding sites on the remaining available receptors. Repeated stimulation leads to fewer and fewer receptor sites available for acetylcholine binding, leading to fatigue and weakness (contrast this to Lambert-Eaton syndrome, in which weakness improves with activity).

Presentation: fatigue, progressive weakness with repetitive activity with ocular symptoms often as the first manifestation and ocular muscle weakness as a first sign in up to 40% (i.e. ptosis, diplopia, blurred vision). Symptoms typically worse at the end of the day. Pay particular attention to bulbar involvement leading to dysarthria and dysphagia. Respiratory failure is rarely a first presentation but does happen. Furthermore, the patient may not manifest normal signs of impending respiratory failure, such as accessory muscle use, so look for other features, such as tachypnea. Also, be aware of patient’s with myasthenic crisis, defined as respiratory failure leading to mechanical ventilation. It occurs in 15-20% of patient’s, usually within the first 2 years, typically with an underlying provocative event (i.e. infection, non-compliance, medication change or new medication, etc.).

Diagnosis: edrophonium stimulation test (less often used) or the ice bag test, serologic testing for anti-ACh-R or anti-MuSK (probably not done in the ED). Most importantly, ALL patient’s with a history of myasthenia gravis should get respiratory parameters (FVC and/or NIF) regardless of reason for presention. Importantly, search for underlying processes that might have led to the exacerbation (i.e. infectious work-up, thorough history to include medications, recent medication changes, etc.)

Treatment: ABCs! As with anything, focus on the things acutely that can kill the patient, such as respiratory failure. Non-invasive ventilation (i.e. BiPAP) can be tried, but this should be done in conjunction with close monitoring and serial respiratory parameters (typically every 2 hours). Neostigmine or pyridostigmine can be given but may increase secretions and worsen weakness or even stimulate myasthenic crisis. As such, they are typically avoided in the acute period, as patients with respiratory failure or impending failure benefit most from plasmapheresis or IVIG with the addition of steroids. Treat associated exacerbating causes (i.e. infection, etc.)

Other things that may benefit the patient that we will not be involved in include thymectomy for those with thymoma and consideration for thymectomy in those without thymoma but <60 years old as well as immunosuppressant drugs, which patient’s presenting to the ED may already be on. Also critical is knowing what drugs to avoid.

Multiple Sclerosis

Epidemiology: peak age of onset is 25-30 years old, women > men with proposed genetic and environmental factors. More common in temperate climates.

Pathophysiology: proposed mechanism is that of an autoimmune disease with autoreactive T cells stimulated by environmental (i.e. viral infection or superantigen) leading to inflammatory response involving CNS demyelination in the brain and spinal cord.

Presentation: optic neuritis may be the initial presenting symptom with painful unilateral vision loss affecting the central vision. Other symptoms are variable, as white matter anywhere in the brain and spinal cord can be involved to include motor, sensory, and bulbar complaints as well as neurocognitive complaints such as poor memory, distractibility, etc. Bowel and bladder dysfunction are common. Uhthoff’s phenomenon (temporary worsening of signs/symptoms secondary to an increase body temperature, such as a hot bath). A comprehensive neurological exam is key

Diagnosis: key to the diagnosis is description of TWO different neurological complaints at different times (i.e. neurological complaints scattered in time and space). CSF studies are abnormal in 90% of cases, with 50% having pleiocytosis, 70% with elevated IgG gamma globulin level, and the presence of IgG oligoclonal bands and/or myelin basic protein. Importantly, IgG oligoclonal bands may also be seen in other disorders, such as neurosyphillis. If sending off CSF studies, send off serum oligoclonal bands at the same time.   Gadolinium enhanced MRI is also important in the work-up. Lesions are bright on T2 signal or FLAIR and are commonly found in the periventricular white matter.

Treatment: for our purposes, acute exacerbations require HIGH DOSE intravenous methylprednisone. Long-term treatment may include interferon-beta, glatiramer, or other immunosuppressant medications. Many patients require baclofen (orally, intrathecally) for spasticicty, and pain is managed with a range of medications. Amantadine may help with fatigue.

Two other disease topics discussed during conference included amyotrophic lateral sclerosis (ALS) and Parkinson’s disease. While important, we don’t often see these present as primary complaints, obviously, but rather patient’s present with complications of the underlying disease. Briefly, ALS is a progressive disease involving destruction of the upper and lower motor neuron units, leading to muscle atrophy and weakness. Ultimately, patient’s often succumb to respiratory failure or other complications such as aspiration pneumonia and other infectious processes. Parkinson’s disease is caused by loss of pigmented dopaminergic neurons in the substantia nigra and development of Lewy bodies leading to symptoms to include tremor, (cogwheel) rigidity, akinesia, and postural instability. The most common reasons for patients presenting to the ED include infection, trauma (think falls), cardiovascular and cerebrovascular events, gastrointestinal complaints, and electrolyte abnormalities. Orthostatic hypotension is a common reason for falls and can be secondary to medication side effects. Treatment really depends on the underlying cause for the presentation. An important point brought up by Dr. Kman is that drugs (i.e. antipsychotics) can lead to Parkinsonian features (or Parkinsonism) and are managed in a different manner.

The pupils are fixed and dilated. The pupils are fixed and dilated?!

Written by Zach Adams, OSUEM resident // edited by Michael Barrie, OSUEM Assistant professor

EMS brings in an unconscious man. They are bagging the patient in the hallway of the ED and tell you that they found the patient “down” at home, unresponsive, and with agonal respirations. The patient is obviously altered, unresponsive, and not protecting his airway. You and the team respond rapidly, performing rapid assessment on this undifferentiated patient. Rapid sequence intubation is performed to protect the airway, and you go down your algorithm. The patient was not moving spontaneously, and you’d like to assess pupillary status. But he’s intubated, sedated, and just received etomodate and rocuronium. The pupils appear dilated and unresponsive. But is the pupil exam reliable after a paralytic?

Continue reading

Intern Review – Can CT Angiography Rule Out Subarachnoid Hemorrhage?

The bottom line – CTA may be able to reasonably exclude SAH when pre-test probability is relatively low and LP is non-diagnostic.

A 55 year old male with PMH significant for HTN and DM presents with new onset worst headache of his life.  He is hemodynamicly stable and physical examination is without focal neurologic deficit.  You suspect SAH and proceed with non-contrast CT head which is negative.  An LP is attempted but fails.  What are your options?

Given the significant morbidity and mortality of this condition and up to 10% are misdiagnosed on initial visit to the ED (1, 2), a careful workup is warranted when to rule out SAH.

The sensitivity for detecting SAH with a non-contrast head CT decreased with time:

  • <6 hours – 100% (3)
  • 6-12 hours – 98%
  • 12-24 hours – 93% (4)
  • 24 hours to 5 days – <60%

After 10 days, subarachnoid blood is resorbed and the study becomes useless (5).  When CT is negative, the next move is an LP to look for RBCs and xanthrochromia in the CSF.  CSF xanthrochromia takes about 2-12 hours to develop but can be detected for up to 3 weeks or longer (6, 7).  In one study, however, traumatic taps may produce a false positive report if not processed within 2 hours of CSF collection (8).

When the CSF is analysed, the RBC count in the 3rd or 4th tube is used to make the diagnosis.  While no specific cutoff exists for the number of RBCs that may constitute a negative tap, a reduction of RBCs by 25% from tubes 1 to 4 is sometimes used.  A recent publication does suggestion that less than 2000 RBCs and no xanthochromia is sensitive enough to rule out SAH (12). This method, however, may itself be folly to definitively say no SAH exists, as at least one study has shown this reduction in RBC count may occur when in fact an SAH is present (9).  Therefore, only a negative CT and LP combined can reliably rule out the process, a process that that has improved with the newer generation CT scanners (10).

Back to our case.  So what do we do when we can’t obtain an LP?  In a small study of 116 patients, CT angiography was used in combination with CT and LP for the diagnosis of SAH (11).  in this study, CT angiography added diagnostic utility to a negative CT and LP by finding 2 cases that would have been missed by a negative CT and LP alone.  So what about just doing CT and CTA?

In a study published in Academic Emergency Medicine in 2010, a mathematical probability model using a pretest probability of 15% or less for SAH (acute-onset headache, non-focal neurological exam) was utilized to determine posttest probability of excluding aneurysmal or AVM related SAH with CT/CTA alone.  In this model, combining CT/CTA was able to exclude SAH with a 99% posttest probability.  Mathematically, the pretest probability for a negative CT/CTA with LP puts the risk of a missed SAH at less than 1%.

Why not just do CT/CTA then for everyone?  For the majority of individuals whom we are considering SAH as a diagnosis, the pretest probability is higher than the aforementioned study for an ED population.  Simply relying on a CT/CTA alone therefore puts us a risk of missing some of the lower risk patient population.  That said, it is likely a reasonable strategy in those unable to undergo LP or will not consent to the procedure.  An alternative in our case might be to perform an fluoroscopic guided LP – as long as the resources are available.  Using ultrasound could potentially improve LP success when landmarks are not easily palpated. When these options are not available, ordering a follow up CTA is a reasonable next step.  At least then you may be reassured that the inability to get an LP decreases the overall chances of missing something sinister.

Written by Dr. Daniel “Zach” Adams, Intern at OSU EM.

Edited by Dr. Michael Barrie, Assistant Professor at OSU EM.


  1. Vermeulen MJ, Schull MJ: Missed diagnosis of subarachnoid hemorrhage in the emergency department.Stroke 38: 1216, 2007.
  2. Kowalski RG, Claassen J, et al: Initial misdiagnosis and outcome after subarachnoid hemorrhage. JAMA291: 866, 2004.
  3. Perry JJ, et al. Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study. BMJ. 2011; 343:d4277.
  4. van Gijn J and van Dongen KJ, The time course of aneurysmal haemorrhage on computed tomographs. Neuroradiology. 1982; 23:153-156.
  5. Al-Shahi R, White PM, et al: Subarachnoid hemorrhage. BMJ 333: 235, 2006.
  6. Chalmers AH, Kiley M: Detection of xanthochromia in cerebrospinal fluid. Clin Chem 44: 1740, 1998.
  7. Sidman R, Spitalnic S, et al: Xanthochromia? By what method? A comparison of visual and spectrophotometric xanthochromia. Ann Emerg Med 46: 51, 2005.
  8. Graves P, Sidman R: Xanthochromia is not pathognomonic for subarachnoid hemorrhage. Acad Emerg Med 11: 131, 2004.
  9. Heasley DC, Mohamed MA, Yousem DA: Clearing of red blood cells in lumbar puncture does not rule out ruptured aneurysm in patients with suspected subarachnoid hemorrhage but negative head CT findings. Am J Neuroradiol 26: 820, 2005.
  10. Boesiger BM, Shiber JR. Subarachnoid hemorrhage diagnosis by computed tomography and lumbar puncture: are fifth generation CT scanners better at identifying subarachnoid hemorrhage?. J Emerg Med. 2005 Jul. 29(1):23-7.
  11. McCormack RF, Hutson A. Can computed tomography angiography of the brain replace lumbar puncture in the evaluation of acute-onset headache after a negative noncontrast cranial computed tomography scan? Acad Emerg Med. 2010 Apr;17(4):444-51.
  12. Perry JJ, et al. Differentiation between traumatic tap and aneurysmal subarachnoid hemorrhage: prospective cohort study. BMJ. 2015 Feb 18;350:h568. [Free open access article]