The triage note read “altered mental status.” I can see why they thought so. The patient didn't open his eyes, giving the impression he was lethargic. He remained this way throughout the interview, but was able to answer questions and follow commands appropriately. No real alteration in mentation.
His records revealed a history of metastatic prostate cancer with involvement of vertebral bone. His old peripheral smears were indicative of refugees forced from their homeland: nucleated RBCs, teardrop RBCs, and a little sprinkling of every less mature and deviant cell type forced out of the marrow at an early age. A hematology consultant previously dictated that he had a form of myelodysplasia.
He said he had been feeling generally weak for two days. Strength testing of his upper and lower limbs proved to be 5/5, however, and he had normal reflexes and down-going toes.
When asked if he would open his eyes, and look at us, he said, “No.” He could not.
This was pretty dense and symmetric ptosis. When we peel his eyelids back, we notice his pupils are reactive bilaterally, and his globes appear normal to inspection. But on ocular motion testing, he cannot abduct either eye.
Bilateral abducens nerve palsies? Possibly from increased intracranial pressure compressing the nerves down against the base of the skull? His ptosis is unlikely to represent bilateral, complete oculomotor nerve palsies, however, because pupillary reaction and adduction of both eyes were conserved.
Normal visual acuity and no afferent papillary defect. II is functional. No sensory deficits to light touch over his face. V is intact. Clear speech, no facial droop, and no discernible dysarthria when conversing.
“Say ‘ma, ma, ma,’” I say.
“Ma, ma, ma.” VII working.
“Say ‘la, la, la.’”
“La, la, la.” XII firing.
“Say ‘ca, ca, ca.’”
“Nga, nga, nga.”
Nga, nga, nga? His palate seemed to rise symmetrically, but “nga, nga, nga” is not normal. He has dysphonia from posterior pharyngeal and palatal soft tissue paresis. IX or X are out.
I wonder if cranial nerves are being picked off indiscriminately as they pierce through inflamed meninges. So we perform an LP for meningitis. The fluid appears clear.
Inspection. He is breathing at 30 times a minute. No supraclavicular, intercostal, or subcostal retractions visible despite his slender build. During inspiration, as the chest wall moves out creating negative pressure in the thoracic cavity, alveoli fill with air, and the parenchyma expands to meet the underside of the thorax. No dimpling of skin between ribs due to lagging, poorly compliant lung tissue below. No retractions.
One concerning feature, though: Each time he inhales and his chest wall expands outward, his abdominal wall bows inward. With inspiration, his diaphragm should contract and depress into the abdominal cavity, displacing abdominal viscera inferiorly and out. In so doing, the abdominal wall should move outward in step with the chest wall. Not so in this case. His abdominal motion was paradoxical.
ABG. The patient has a pH of 7.38 and pCO2 of 45. Looks good on paper, but in real life, it is not so reassuring. Compared with his respiratory rate of 30, his pCO2 should be much lower. The volume of air he is moving with each breath must be low. No evidence of a prolonged expiratory phase or wheezing to suggest CO2 dense air trapped in alveoli distal to collapsing bronchioles. So he is not retaining. The worrisome pCO2 of 45 despite tachypnea is representative of a restrictive ventilatory defect from diaphragmatic fatigue seen as paradoxical abdominal wall movement at the bedside. C3, 4, 5 out.
The lumbar puncture results show elevated protein but a normal cell count. I had been quite focused on indiscriminant inflammation of nerves in transit through inflamed meninges. But this synthesis is inadequate now. I must take a step back, and start from the top.
Cerebral cortex. Quite unlikely to have such focused pharyngeal and ocular muscle weakness from the motor strip bilaterally, with no involvement of the nearby hand area on the homunculus, and no deficit in speech centers.
Corona radiata and internal capsule. Again, discrete weakness points away from lesions here, where a large number of important motor axons are funneling into a tighter and tighter space as they move inferiorly. I would expect some involvement of the limbs and lower face.
Basal ganglia. The caudate, putamen, globus pallidus, and other associated subcortical grey matter are outside the pyramidal motor tracts and concerned mostly with the coordination of motor function. He demonstrates no such dysregulation of motor execution. No extra-pyramidal signs.
Midbrain, pons, medulla. Although he has multiple deficits of bulbar muscles, I cannot localize his findings to one lesion within the brainstem. To have both VI nuclei or tracts out without any involvement of the corticospinal axons or the VII nerve nucleus or fibers running millimeters away would be an awfully fine lesion unilaterally. And almost impossible bilaterally. The same reasoning for the IX and X nerves bilaterally. Not to forget that ptosis alone does not make a complete III deficit, and that motor nuclei corresponding to C3, 4, and 5 are not to be found here.
Nerve. So we move out of the brainstem to the periphery: cranial and cervical nerves. Composed of epineurium lining a bundle of fascicles, within which run multiple axons. Each axon covered by endoneurium and myelin sheaths that are the extension of Schwann cells.
A compressive neuropathy of both VI nerves by elevated ICP would not explain the other deficits he has. But multifocal axonal degeneration unrelated to compression should remain on the differential.
Demyelination could result in bilateral, symmetric dysfunction of both cranial and cervical nerves. The acute demyelination we call Guillain-Barré syndrome. The specific rostral to caudal progression termed the Miller Fischer variant. But one part did not fit. With adduction and pupillary responses preserved, he did not have complete III dysfunction. Although not perfect, demyelination should remain high on the differential. After all, relative III pathology may still allot for adduction of either eye if the counterbalancing VI nerves are densely deficient. And he did have albumino-cytologic dissocation in his CSF.
Neuromuscular junction. His presentation certainly fits. Pure motor disturbances with no sensory findings. Small ocular and bulbar muscles first affected, now progressing to diaphragm paresis. An antibody attack on the Ach receptor at the muscular endplate of the junction: a myasthenic crisis?
Think briefly about antibody attack to the presynaptic component of the NMJ. If Ach release were inhibited, we would expect autonomic findings in addition to muscular weakness because the physiology of these lesions affects both the NMJ and the Ach-dependent interaction between preganglionic and postganglionic neurons of the parasympathetic and sympathetic system. His pupils, however, were normal, his mouth was not dry, he was not retaining urine or stool, and he was not hot or red. So I favor an assault on nicotinic receptors on the motor endplate over an attack on the proximal neural release point.
Muscle. Myopathy could be from disruption to any component of the contractile process or sarcolemmal membrane, or a disturbance of the voltage or ligand gated channels responsible for sarcolemmal depolarization and cytoplasmic calcium release. Alternatively, myositis would be direct inflammation of muscles during an infectious or autoimmune incident. But the distribution of his weakness did not imply a primary muscle disorder, his CK was normal, and his potassium level did not suggest a channelopathy. I take a step back to NMJ.
The furthest I could get was warfare at the motor endplate of the NMJ. It was the cleanest explanation. With a history of metastatic carcinoma and marrow dysfunction, a deranged, misguided immune system seeking out prostatic neoplastic cells and inadvertently directing their attack at a molecular mimic in the form of nicotinic receptors did not seem too farfetched to me.
A missing piece. Not surprisingly, his weakness progressed later in his course, and he ended up intubated in the medical ICU, but not before our neurology consultants were able to get an important historical feature from him: He ate a lot of honey. With rapid clinical progression and this historical fact, they had a diagnosis.
Although most cases of botulism are from infected wounds or ingesting preformed toxin in certain foods, there is an adult version similar to the infantile presentation predicated on ingestion of spores, possibly via raw honey, with the organism living in intestinal mucosa. Our patient, with his impaired immune function, could have obtained this type of botulism in the same manner as a younger host with immature intestinal mucosal immunity.
Warfare at the NMJ? Yes. Attack on the nicotinic receptor? No. Botulinum toxin is actually directed at the presynaptic side. Why no autonomic findings? I cannot say. Maybe the findings were missed, or the rules just don't pan out. Or maybe as emergency clinicians, we are afforded only one glimpse at a dynamic process whose full manifestation has yet to come.
Comments about this article? Write to EMN at email@example.com.
Dr. Morchi is the director of the Medical Screening Examination program at Harbor UCLA Medical Center and an assistant professor of emergency medicine at UCLA's David Geffen School of Medicine.
Read all of Dr. Morchi's past columns in the EM-News.com archive.
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