Week 8: Neuro. pt 1

Periodic paralysis is a rare neuromuscular disorder related to a defect in muscle ion channels. There are several types of periodic paralysis: hypokalemic, hyperkalemic, and thyrotoxic. The hallmark of periodic paralysis is painless muscle weakness precipitated by heavy exercise, fasting, stress, high-carbohydrate meals, or in the case of hyperkalemic periodic paralysis, consumption of potassium rich foods. Hypokalemic periodic paralysis occurs typically in the first or second decade of life and will last from hours to days. It is caused by an autosomal dominant defect in calcium or sodium channels on the membranes of myocytes. Diagnosis can be made with a basic metabolic panel in the presence of paralysis. The potassium level will be < 3.5 mEq/L. A transtubular potassium gradient ((UK+ x POSM) / (UOSM x PK+)) can also be used to diagnose hypokalemic periodic paralysis , a value < 3 mEq/L is highly suggestive of hypokalemic periodic paralysis (normal range is 8 to 9 mEq/L). Hypokalemic periodic paralysis is more common in men and can be treated with carbonic anhydrase inhibitors or potassium-sparing diuretics.

An edrophonium test (C) is used to diagnose myasthenia gravis, a neuromuscular disease causing muscle weakness due to antibodies that block acetylcholine receptors at the postsynaptic neuromuscular junction. Edrophonium blocks the breakdown of acetylcholine by inhibiting acetylcholinesterase, thereby temporarily reversing the weakness caused by myasthenia gravis. This test is rarely performed due to the potential of life threatening bradycardia. Magnetic resonance imaging of the brain (D) is helpful in the diagnosis of multiple sclerosis, a demyelinating disease of the brain and spinal cord characterized by neurologic deficits that change over time, but plays no part in the diagnosis of hypokalemic periodic paralysis. Cerebrospinal fluid (CSF) protein and cell count (B) are useful in the evaluation of Guillain-Barré syndrome (GBS), a rapid-onset ascending paralysis resulting from autoimmune damage to the peripheral nervous system nerves and myelin. Common causes are recent infection, upper respiratory infections, or gastroenteritis with Campylobacter jejuni. Cytomegalovirus has also been linked to GBS, but up to a third of cases of GBS are idiopathic. Treatment is supportive and includes airway protection if the paralysis rises to the level of the diaphragm. CSF analysis will show an elevated protein level with low numbers of white blood cells.

In the emergency department intubating a patient with a NM disease is made less on hard numbers and more on the patient’s overall clinical picture. However, guidelines do exist for these disorders which indicate that an elective intubation should be performed. The Negative Inspiratory Force (NIF)  or Maximal Inspiratory Pressure (MIP) test is one we can perform in the ED if we ask RT for assistance. As the name implies it measures the force of inhalation, it is measured in terms of “negative” values, and >-30 cmH2O indicates the need for likely intubation. FVC (B) is also a metric that can be used, however the normal FVC for an adult ranges from 3,000-5000 mL. There is not a hard indication for intubating a NM disease patient based on PCO2 (C) alone. While 47 is slightly elevated, it is not an isolated reason to intubate this patient. While requiring previous intubations in the past (D) may increase this patient’s risk for respiratory failure, it is not an indication to intubate.

Other metrics for respiratory failure in patient’s with NM disease:

FVC: A forced vital capacity is the total volume exchanged from maximal inhalation/exhalation (i.e. the biggest breath you can take). An FVC less than 15-20 mL/kg in the sitting position. The normal adult human has an FVC of about 3,000-5,000 mL.

NIF or MIP: Maximal negative pressure generated on inspiration. It is an indirect measure of the diaphragm’s force. In general values > -30 cmH2O (i.e. between 0 to -30) should raise concern for impending respiratory failure. For reference, -60 cmH2O is equivalent to “a weak cough” and predicts some difficulty with clearing secretions, and normal is < -100 cm H2O

MEP: Maximal expiratory pressure, which is the opposite of the MIP or NIF as it measures the expiratory force. In general values < 40 cm H2O is a worrisome sign of respiratory failure.

*In concert the above three values comprise the “20-30-40” rule: FVC <20mL/kg, MIP >-30 cmH2O, MEP >40 cmH2O. These parameters are NOT hard and fast rules… they are guidelines and should never override a strong clinical inclination to intubate.

Progressively worsening respiratory acidosis

Inadequate clearing of secretions

Clinical respiratory distress

Cauda equina syndrome is a neurologic emergency and is the result of external compression of the cauda equina by a tumor, abscess, herniated disc, expanding hematoma, or other mass. Because the cauda equina is composed of spinal nerve roots, compression results in a peripheral neuropathy as opposed to a central neuropathy. Signs and symptoms include back pain, urinary retention (measured by a post-void residual bladder volume usually > 100 cc), overflow urinary incontinence, saddle or perianal anesthesia, and lower motor neuron findings such as lower extremity hyporeflexia and flaccidity, which are usually unilateral. Patients with findings concerning for cauda equina syndrome need emergent neurosurgical consultation and advanced imaging with MRI.

Conus medullaris syndrome is another neurosurgical emergency that may present with similar features as cauda equina syndrome, including saddle anesthesia and bladder incontinence. However, because the conus medullaris is the terminal spinal cord and, by definition, a central structure, exam findings will be consistent with upper motor neuron deficits such as lower extremity hyperreflexia or a positive Babinski sign (upgoing toes). A positive straight leg raise test indicates sciatica.

Botulism is a neuromuscular disorder caused by Clostridium botulinum. Through a toxin-mediated process, the release of acetylcholine is inhibited, leading to muscle weakness and paralysis. Classically, botulism causes a symmetric descending paralysis. Cranial nerves and bulbar muscles are often the first to be affected. As the disease progresses, patients can develop respiratory failure through paralysis of respiratory muscles. Patients will typically present with diplopia, dysarthria, and dysphagia. On physical exam, patients with often have dilated pupils that are nonreactive to light. In adults, botulism can occur after the ingestion of canned foods contaminated with Clostridium botulinum. Symptoms typically present within six to 48 hours of exposure to the toxin.

An ischemic stroke can present with signs and symptoms similar to botulism. However, a history of recent ingestion of canned food product and nonreactive dilated pupils is most consistent with botulism, also given this patient’s age a stroke is far less likely. Myasthenia gravis  is a neuromuscular disorder caused by antibodies that lead to ineffective acetylcholine at the neuromuscular junction. It can present similarly to botulism, but symptoms of botulism will develop more rapidly. Also, patients with myasthenia gravis will have reactive and normal-appearing pupils. Scrombroid poisoning is associated with larger game fish such as tuna, and causes a histamine reaction including flushing, headaches, blurred vision, cramping abdominal pain, and GI upset.

This patient presents with a radial neuropathy also called “Saturday Night Palsy.” The radial nerve arises from the C5-T1 roots. It controls extension of the fingers, thumb, wrist and elbow. Symptoms of radial neuropathy depend on the location of compression. Compression in the axilla (typically from improper use of crutches) causes weakness of extension at the elbow, wrist and fingers. More typically, the nerve is compressed between the humeral shaft and another hard surface and results in weakness with extension at the wrist and fingers. This typically occurs from deep sleep (often secondary to inebriation). About 90% of radial nerve mononeuropathies that occur during sleep, coma or anesthesia recover within 6-8 weeks. Patients should be placed in a wrist splint with 60 degrees of dorsiflexion to prevent atrophy and contractures.

Radiographic imaging and pain control are not necessary as the patient does not have any concerning physical exam findings or history of trauma. Activation of stroke protocol would be inappropriate for several reasons. He is outside of any TPA window as he awoke with these symptoms, the symptoms are consistent with a nerve palsy, and his NIHSS scale is low (likely just a 1 for his sensory deficit). Consultation of neurology and MRI of the brain is not needed emergently as the patient has a clinical diagnosis of a radial nerve palsy, he can follow up as an outpatient.

Peripheral Neuropathies
• Sciatic: buttock injury, hip dislocation, ↓ knee flexion, foot drop, rx: analgelsics, physical therapy,
• Common peroneal: proximal fibula injury, footdrop, rx: ankle splint
• Radial: crutches, wrist/finger drop, rx: wrist splint
• Ulnar: elbow injury, ↓ finger adduction/thumb grasp, 4th/5th digit paresthesias
• Lateral femoral cutaneous: inguinal ligament entrapment, upper thigh dysesthesia/numbness

MRI is the diagnostic modality of choice for multiple sclerosis (MS). Multiple sclerosis is characterized by demyelination of axons within the central nervous system. Patients present with symptoms that are “scattered in time and space” meaning that they have intermittent symptoms in anatomically disparate locations. Patients may have patchy motor and sensory deficits and bladder dysfunction. Spinal cord lesions typically involve the posterior columns, lateral spinothalamic tracts and the corticospinal tract. Spinal MRI is the diagnostic modality of choice because it can be used to rule out causes of cord compression while also showing lesions diagnostic for MS.

CT scan may be performed but is NOT a diagnostic test for MS. Carotid duplex scans are used when there is concern for TIA, not in MS. CSF oligoclonal bands are helpful in the diagnosis of MS, but are not the diagnostic test of choice, furthermore serum oligoclonal bands are of no help.

The patient is most likely suffering from Guillain-Barré syndrome, a progressive, ascending demyelinating polyneuropathy that typically begins with lower extremity weakness. Classically, GBS presents with symmetric lower extremity weakness, decreased or absent deep tendon reflexes, and little or no sensory involvement (although variable). It follows a respiratory or gastrointestinal infection by weeks to days. Common organisms implicated include Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, and Mycoplasma pneumoniae. Elevated protein with only a mild pleocytosis on cerebrospinal fluid analysis (termed albuminocytologic dissociation) is highly specific in the clinical setting of suspected GBS. Patients with probable GBS should receive a neurology consult and be admitted for either intravenous immunoglobulin (IVIG) therapy or plasma exchange. Both IVIG and plasma exchange have been demonstrated to be more effective than placebo has, but no advantage is incurred upon administration of both therapies. Neither therapy has been proven more effective than the other.

 The edrophonium test is used for myasthenia gravis, not for GBS. Corticosteroids alone are no longer recommended, but IV steroids coadministered with IVIG may speed recovery. Regardless, steroids have no role in the diagnosis of GBS. Pleocytosis and oligoclonal bands of immunoglobulin G is characteristic of MS

This patient has myasthenia gravis, caused by antibodies to the acetylcholine receptor (AChR) at the neuromuscular junction. Failure to respond to acetylcholine stimulation leads to decreased muscle fiber activationand muscle weakness. The antibodies cause AChR degradation, dysfunction, and blockade. Ptosis and diplopia are most commonly the first symptoms. Patients may also experience dysphagia, proximal muscle weakness, and dyspnea. A full myasthenic crisis may lead to respiratory failure due to flaccid paralysis of the muscles of respiration.

Botulinum toxin inhibits acetylcholine release at the synapse (B). It is produced by Clostridium botulinum, an anaerobic spore-forming bacterium. C. botulinum occurs naturally in the soil and causes human disease when ingested. Botulism is associated with a descending symmetric paralysis. Amyotrophic lateral sclerosis (ALS) is caused by a mutation of superoxide dismutase (C) leading to an abnormal response to stress and cell death. Central and peripheral nerves are affected with sparing of sensory and cognitive function. Initial symptoms are muscle weakness, atrophy, fasciculations, dysarthria, and dysphagia. Parkinson’s disease is associated with depigmentation and dopaminergic neuron loss (D) in the midbrain, especially the substantia nigra. It is also characterized by Lewy bodies, which are cytoplasmic inclusions seen under the microscope. Parkinson’s disease is characterized by tremor, cogwheel rigidity, bradykinesia or akinesia, and postural and equilibrium impairment.

Normal pressure hydrocephalus (NPH) is characterized by the following characteristics: wet, wacky, and wobbly. More specifically, it includes a triad of progressive dementia, ataxia and urinary frequency or incontinence. It is a reversible cause of dementia and results from defective uptake of CSF. Head CT will reveal ventricular enlargement. Atrophy may occur in chronic alcoholics or the elderly, but is neither sensitive nor specific for NPH. A brain mass can cause a variety of symptoms, but headache with a neurologic deficit would be a more common presentation

A patient in myasthenic crisis should receive immunomodulatory therapy. This includes either IVIG or plasmapharesis. The decision to start either should be made in concert with a consulting neurology service. The literature does show a benefit of IVIG over placebo, however the difference in IVIG vs. plasmapharesis is unclear. In general, if resources are available, plasmapharesis is preferred as it directly removes the AChR ab from the blood, whereas IVIG acts by both binding harmful ab, as well as downregulating the patient’s immune response. This is a costly medication and requires repeated doses.

Pyridostigmine and neostigmine are used orally for outpatient maintenance and not for acute crisis. They act by inhibiting AChE, increasing the amount of ACh at the NMJ. The IV dose might cause complications from the cholinergic excess such as increased secretions. Rituximab is not a first line treatment in MG, though it may play a role in outpatient therapy by decreasing the production of ab from B-cells. Edrophonium is used for the diagnosis of MG, and this patient already has established MG. It is a short-acting AChEi . Administration in patients with MG should lead to decreased symptoms in 30-90 seconds. Use of edrophonium can result in potentially significant complications, such as symptomatic bradycardia and bronchospasm. These effects can be reversed with atropine. It should be used with caution, if at all, in older patients, those with asthma/COPD and those with underlying cardiac disease.