Motor Neuropathy – additional opinion
Short Summary

53-year-old male with lower motor neuropathy affecting all 4 limbs. The neurologic examination showed left limb hyposthenia, left upper limb hypotrophy and diffuse fasciculations. The patient was diagnosed with “suspect motor neuron disease" and was treated with IVIG cycles with slight initial improvement, but later lack of response and worsening of the clinical condition. In the expert's opinion, the initial response to combination of IVIg and steroids is supportive of multi-focal motor neuropathy, and it is recommended to continue the IVIg and the riluzole, and to start folate supplements.

 

Patient's Questions
1)        Diagnostic picture:
a.         Motor neuron disease.
b.         Chronic polyneuritis
c.         Other not classified
2)         What do you think could be the best treatment?
Medical Background

Age: 53 Sex: male
Medical History:
Appendectomy at 5 years old.
At 10 years old post-trauma fracture of left clavicle.
In 1984 and in 1985 post-trauma fractures of left foot.
 
Case history:
In September, 2007 left lower limb and left upper limb hyposthenia with mainly distal motor clumsiness. Appearance, furthermore, of left upper limb hypotrophy and diffuse fasciculations all over his body, in particular after an effort.
Following the advice of a specialist in neurology, the patient has performed on 12/2007 an MRI of the brain (within normal limits) and an MRI of overall rachis (posteromedian disc protrusion C4-C5; total disc protrusion C6-C7; left paramedian posterior disc hernia L1-L2; posterior disc protrusion L4-L5. Thin hydrosyringomyelic cavity at the dorsal marrow level in the D6-D7 segment. No enhancement after contrast medium).
A neurological specialist’s examination was, therefore, performed as well as Day Hospital at theout-patients Department for Motor Neuron Diseases on 01/2008; during the Day hospital a sample was taken for thyroid function test, estimation of neoplastic markers, antigangliosides antibodies, auto-antibody asset and genetic investigation for SOD 1 (see enclosed documentation no. 1).
Further hospitalization at University Neurology Unit II of the Hospital of Bari for diagnostic completion and, so, the patient was dismissed with diagnosis of “suspect motor neuron disease”. A few days later a neurological specialist's examination was performed. It advised, considering the not perfect diagnostic definition, the ANA positivity in serum and the anti-borrelia Igm in serum, as well as CSF immunoblotting finding of “G type Paraproteinemia” and the increase to the standard CSF-serum albumin quotient, a therapy with Rilutex 1 tablet x 2 daily, Rigentex 400 mg 1 tablet x 2 daily, Deltacortene 25 mg ½ tablet daily for 15 days followed by ¼ tablet for the next 15 days plus IVIG cycles with reported improvement (< frequency) of cramps and fasciculations.
The disease follows a progressive course and the patient shows, at present, a left “hackney gait”.
At the neurological visit on September 2008 there are proofs of:
-           at the inspection - evocable, spontaneous, widespread fasciculations at percussion; significant hypotrophy of the proximal muscles of the left upper limb. Subjective gradual strength reduction.
-           at the neurologic examination :
o          Nothing on the cranial nerves (with the exclusion of a light congenital strabismus)
o          muscle tone within normal limits
o          Proximal hypotrophy especially on the left upper limb; lumbrical and interossei hypotrophy more evident on the left side
o          Osteotendinous reflex within normal limits.
o          Mingazzini within normal limits
o          Abdominal reflexes: light reduction on the left side more evident at the epigastric level
o          Babinski negative bilaterally
o          Complete sensitivities.
Noteworthy examinations performed
Immunologic examinations (1/08):
Positive ANA with a titer of 1/320
IgG subclasses IgG4           3.69 (n.v. (normal values) 0.08 – 1.40)
CPK 444 (n.v. 35 – 232)                 
 
CSF analysis (2/08):
ALIQUOT 1:                                                                          N.V.:
Appearance              clear                                                   clear
Colour                                    lightly hematic                                   colourless
RBCs                         659/mmc                                            absent
WBCs                         10/mmc 100% lymphocytes            <5
proteins                      58 mg/dL                                            <40
glucose                      55 mg/dL                                            35-65 
CSF glucose/serum             0.65                                                    >0.6
lactate                        14.5                                                    10 – 22
 
ALIQUOT 2:
Appearance              clear                                                   clear
Colour                                    colourless                                          colourless
RBCs                         325/mmc                                            absent
WBCs                         11/mmc 100% lymphocytes            <5
 
Evoked potentials (08/08 only conclusions):
Negative SEP and MEP
 
EMG (08/08 only conclusions):
Signs of denervation in the muscles of the four limbs.
EMG findings within the limits in the right masseter muscle.
The first sensory nerve cell is complete.
Normal motor conduction untill the Erb’s point of the examined nerve trunks to the upper limbs, normal lantencies of the recurrent responses (F wave).
Within the normal limits is the motor conduction to the lower limbs where a fall of amplitude of the M answer in proximal site on the left deep peroneal nerve is reported, this to be related to an abundant denervation and at the beginning site of the clinical symptomatology.
All in all, electric findings compatible with the motor neuron disease with signs of denervation within the investigated appendicular muscles (4 limbs) and small signs of reinnervation; no signs of denervation in the right masseter.
MR brain and overall rachis (08/ synthesis):
The study of the pyramidal tract in all his course did not give evidence of signal alterations. In comparison with the previous examination (12/07) reduction of the hydromyelic cavity present at level D6-D7.
Clinical considerations on the course of the illness and on the performed therapy (by the patient’s specialist:
In the outpatient treatment with riluzole and cortisone, the patient underwent the first IVIG infusion taking great advantage from it: moderate functional psychological recovery; the other infusion cycles (when the cortisone treatment was suspended) did not improve the symptomatology.

Expert's Opinion

The serological tests that were repeated exclude the concern about Lyme disease. No need for treatment trial with ceftriaxone.
Low serum folate: Motor neuron disease has not been reported due to folate deficiency. The neurological complications of folate deficiency have been controversial except the fact that folate treatment aggravates the combined system degeneration of B12 deficiency in pernicious anemia. There is suggestion of its role is sensory neuropathy but I seriously doubt this is the etiology of the patients motor neuron disorder. At the same time, oral supplements with folic acid make common sense and are harmless.
Is this sporadic ALS: it may well be the case and best diagnostic test is time and course over the next year: development of upper motor neuron syndrome and brainstem motor dysfunction will establish this diagnosis. The electrical findings are consistent with it including the widespread denervation and normal conduction velocities.
Alternative diagnosis: However ALS is essentially has no treatment at this time. Moreover, there are features in this patient that make us consider other diseases:

CSF: the slight increase in protein, increase in white blood cells are not seen in ALS. The lack of upper motor neuron signs clinically should always make us consider alternative diagnoses. The nerve conduction velocities can be misleading if "inching" techniques are not used and sometimes the difficult proximal nerve stimulation are not performed. The initial response to combination of IVIg and steroids is in fact supportive of multi-focal motor neuropathy, not against it. Because of these issues, I recommend the following:
-       Continue the IVIg for completing the 6 courses as planned.

-       Continue the riluzole for the time being as long the liver tests remain normal. Start folate supplements;

-       Other immunosuppressive treatments for multifocal motor neuropathy: If no response appears after completion of the IVIg courses and if clinical deterioration continues:

-       Suggest repeating the EMG/NCV to see if the NCVs now show conduction block, before embarking on immunosuppressive drug treatment with cyclophoshamide, methotrexate or azathioprine because of the potential serious adverse effects of the drugs.

""