52-year-old male with a one year history of lower motor neuropathy affecting the limbs, left upper and lower limbs clinically and all 4 limbs electrically. The neurologic examination showed left lower and left upper limb hyposthenia with mainly distal motor clumsiness, appearance of 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.
- Motor neuron disease
- Chronic polyneuritis
- Other not classified
What do you think could be the best treatment?
Age: 53 Sex: male. 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.
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 :
- Nothing on the cranial nerves (with the exclusion of a light congenital strabismus)
- muscle tone within normal limits
- Proximal hypotrophy especially on the left upper limb; lumbrical and interossei hypotrophy more evident on the left side
- Osteotendinous reflex within normal limits.
- Mingazzini within normal limits
- Abdominal reflexes: light reduction on the left side more evident at the epigastric level
- Babinski negative bilaterally
- 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
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.
The CSF is abnormal with increase in the white blood cells and protein, not explained by the small number of red blood cells from traumatic tap. I also noted the serological abnormalities of increased IgG and positive ANA. A mention is made of IgM serology for borrelia antibody being positive. I noted the results of other extensive laboratory tests, mostly relevant autoantibodies and other immunological tests. Noted the slight initial improvement with IvIg and lack of response later and worsening of the clinical condition.
There are several features against primary motor neuron disease: lack of upper motor neuron and cranial nerve involvement and the abnormal CSF are particularly important.
Multifocal motor neuropathy: many features suggest this condition, felt to be immune-mediated. Most cases have anti-GM1 antibodies in the serum but were negative in this man. The electrical studies typically show motor conduction block but not all cases; sometimes it is technically difficult to demonstrate on EMG/NCv. Most patients improve and stabilize on IvIg treatment but some progress despite the treatment. This remains a major possibility in this case.
NeuroBorelliosis: I am not familiar with incidence of this infection where the patient lives. It needs further consideration as it is very treatable. Borreliosis can affect the many nerve roots and produce widespread poyradiculaopathy resembling this patient's condition. The serum antibody, the csf pleocytosis and increased protein are important clues.
Recommendations: explore the borreliosis further: Repeat the serum IgG and IgM antibodies and make sure that specific test by Western blot is done. If CSF is available, check the borrelia antibody in the CSF, a strong evidence for neuroborreliosis. If the initial test is indeed positive by Western blot (specific antibody), I would treat the patient with 3 weeks of intravenous ceftriaxone. The treatment is generally well tolerated and is one time measure and I have low threshold to treat empirically with the findings you already have.
If there is no response to this after 3 months or so, multifocal motor neuropathy is the likely diagnosis, other immune treatments may be worthwhile , although here evidence is anecdotal and the treatment have potential for serious side effects. This would be reasonable if the functional status of the patient deteriorates significantly. The most used treatment when IVIg fails, is cyclophoshamide, 1-2 mgs/kg for 6 month trial or monthly pulse doses for 6 months. Both these treatments need to be given by physicians experienced in the use of these drugs. Alternatives with less side effects are azathioppirne and methotrexate. The evidence for efficacy has not been tested in clinical trials for any of these drugs in this form neuropathy.
The small syrinx in the mid-dorsal region seems unrelated to the clinical problem as it cannot explain the upper limb abnormality.