Axonal and Demyelinative Sensorimotor Neuropathy
66-year-old male with a 6-year history of sensory symptoms in the feet and hands. He describes a sensation of cold and stinging in the feet; and numbness in the hands, especially at night. Nerve conduction and EMG demonstrated axonal and demyelinative sensorimotor neuropathy with neurogenic changes in muscles. Follow-up nerve conduction testing that was performed 2 years later showed similar findings.
1) What in your opinion is the diagnosis ?
2) Any other tests that could be done in order to clear the picture ?
3) What is your recommended treatment ?
Patient: male, 66 years old
Diagnosis: Axonal and Demyelinative Sensorimotor Neuropathy
Diagnosis: Axonal and Demyelinative Sensorimotor Neuropathy
Born in Iraq, immigrated to Israel when was 10.
Married +2, accountant.
Works out in a Gym 3-4 times weekly.
Does not take drugs regularly.
No neurological disease in the family.
During the last 6 years has a cold sensation and stinging of feet at night.
Feels numbness in hands at night.
During walking feels difficulty and also has difficulty in writing. After 20 minutes of walking has pain in gastrocnemius and thighs and has to stop. After a rest, pain disappears.
The cold sensation and the stinging of feet and hands ,only at night.
Nerve conduction and EMG preformed 2 years ago have demonstrated axonal and demyelinative sensorimotor neuropathy with neurogenic changes in muscles.
Was hospitalized for work-up including LP which found protein 76.
Laboratory work-up in the direction of collagen disease, multiple myeloma, B12 defienncy, hypothyroidism , VDRL, were all normal.
Following, tests for HgA1c, protein electrophoresis, urine proteins, Cryoglobulins, anti SSA-SSB, anti Hu, Chest CT – all normal.
An expert’s opinion 2 years ago concluded that the diagnosis is:
Axonal sensor neuropathy of unknown reason, without paraesthesias.
It was concluded that there was no need for nerve biopsy because of the very small chance of finding a treatable disease and only follow-up was recommended.
In the last 2 years complaints have not changed much.
New nerve conduction studies were preformed on October 2008. It was concluded that:
“Nerve conduction testing done today showed evidence for predominantly axonal sensorimotor neuropathy with mild demyelinating features in the legs. EMG study revealed mild chronic neurogenic changes in the distal muscles of the right lower extremity. There were not significant changes as compared with the previous study from 12/2006.”
It appears that symptoms in the hands increase with use; and symptoms in the feet increase with walking; there is a component of the history, therefore, that suggests claudication (neurogenic or vascular), since rest ameliorates the foot discomfort. The narrative summary highlights the sensory complaints; and walking difficulty is described in the context of pain. (I assume that pain compromises gait. There is no description of strength per se (or a formal description of gait, Romberg testing or tendon reflexes), so the status of the motor examination is not entirely clear. I am inferring that motor function is relatively normal and that the brunt of the disease process targets the sensory fibers.) The electrodiagnostic findings separated by 2-years are similar: sensory responses are attenuated in the legs, but they are preserved; and motor responses are normal in the arms and markedly reduced in the legs
I suspect the mild to moderate slowing of nerve conduction velocity in the legs might be comfortably explained by axon loss without invoking an additional "demyelinating" process superimposed on the axon loss character of this neuropathy. Fairly extensive laboratory testing has been undertaken and the "usual suspects" have been sought and no clear cause of the polyneuropathy has been identified.
How would one classify the neuropathic process? It is likely that the patient has a chronic, primarily sensory, mixed large and small fiber, predominantly axon loss, length dependent polyneuropathy; it appears to be stable, in a plateau phase (there is no active denervation on needle electrode examination, supporting the indolent nature of the process). If not already done, I would suggest an MRI of the lumbosacral spine to seek evidence for spinal stenosis or root compromise for two reasons:
First, there is a suggestion of claudication and if the peripheral vasculature is normal, then evidence for spinal stenosis should be sought.
Second, I am impressed by the preservation of the lower extremity sensory responses, in fact they are relatively more robust than the motor responses, suggesting a very proximal or root localization of pathology (this is not to say that the diagnosis is not neuropathy, only that there might be an additional polyradiculopathy component). Regarding laboratory studies, the CSF protein is mildly elevated and raises the diagnostic possibility of CIDP, but there is no compelling evidence of acquired demyelination on the EMG.
Common causes of a chronic, axon loss neuropathy, in the absence of a positive family history or stigmata of Charcot Marie Tooth disease (pes cavus and hammertoes) would be toxicity (seen in the context of chemotherapy or xanthomatous neuropathy), metabolic disease (diabetes being far and away the most common cause), the sensory variant of CIDP (for which we do not have electrodiagnostic support and the relative nonprogressive nature of the process would be unusual), paraneoplastic disease and HIV infection (both of which have been excluded). Vasculitic neuropathy may be quite painful, but usually is more aggressive and is notable for a mononeuropathy multiplex presentation, not seen in this case. It would be important to explore whether there is an autonomic component to this neuropathy since there is a strong indication of large and small fiber sensory involvement, and if so, then seeking evidence for amyloid would be important (fat pad biopsy); the presence of small fiber sensory fiber dysfunction -- suggested by the pain and stinging -- leads one to ask if there is compromise of the postganglionic sympathetic fibers, autonomic members of the small fiber population.
Therefore, I would concur with the opinion rendered: that the patient has a chronic sensory predominant, mixed large and small fiber polyneuropathy. I would recommend evaluation for an accompanying autonomic neuropathy and consider a fat pad biopsy looking for amyloidosis. I would follow-up on the clinical suggestion of claudication with peripheral vascular studies and an MRI of the lumbosacral spine. For now, therapy might be directed at management of pain which is often a challenging undertaking, but might include instituting a variety of pharmacologic modalities among them topicals (lidoderm patch), tricyclics (nortriptyline), and anticonvulsants (neurontin or lyrica).