1st and 2nd Motor Neuron Disease of ALS-type
Short Summary

34-old-male had suffered for 8 months from motor function deterioration in the limbs, tongue and palate. He was diagnosed with 1st and 2nd Motor Neuron Disease of the ALS-type. He also underwent accidental fall and traumatic brain injury during his last in-hospital evaluation. The only proven treatment for his condition is Riluzole that may prolong life by few months.

Patient's Questions
1)         Do you share the suspect diagnosis?
2)         As for the diagnosis definition do you think that the medical tests, already performed, and the future rachiocentesis are correct?
3)         Do you confirm the diagnosed therapy?
4)         If you confirm the suspect diagnosis what therapy would you suggest?
5)         Could you give us indications on the superior quality medical and clinical centers in Italy and in Europe?
6)         Prognosis?
Medical Background

Patient's History
Age 34, Sex: Male
Diagnosis1st and 2nd Motor Neuron Disease
From his family doctor’s certification on 07/2008:
-           Discectomy L5-S1
-           Recurrent fasciculations and motor deficit of upper and lower limbs for 8 months
-           Velum palatinum paralysis
-           Chronic sinusitis
-           Turbinate hyperplasia
-           Disontogenesis 9th bilateral upper molar
-           Intraoral sepsis
-           Oral candidiasis
The clinical neurological picture gradually resolves with antibiotic therapy
Reactive depressive syndrome in therapy with duloxetine 60mg.
Case history:
In consequence of the described neurological sintomatology, the patient was hospitalized at the neurology ward of Imperia Hospital and he was discharged in December 2007 with diagnosis of “ probable 1st and 2nd motor neuron disease”. Concerning this, the medical report of the encephalus+cervical spine MRI, with no contrast medium, performed on 12/2007, is reported: “Ventricular system regular in size and morphology. Subarachnoid spaces of basis and convexity within the normal range limits. Signal hyperintensity along the bilateral corticospinal tract from the corona radiata to the medulla oblongata in possible relation with gliotic processes. Signal anomalies on the cervical spinal cord, evident in the bilateral axial sequences but more evident in the right side. Vertebral angioma in C5. The dimensions of the spinal canal are regular. In C5-C6 and C6-C7 modest large scale disc protrusion with dural impression”.
Further tests performed are:
- CT scan of the paranasal sinuses on 07/2008 with notice of “minimum mucus thickenings on the maxillary sinus floor, more evident in the right side; small hypertrophy of the right middle and inferior nasal turbinates. The other paranasal sinuses are clear. No evidence of osseous-skeletal lesions”.
- Dentascan (2 dental arches):
            Upper dental arch: dysodontiasis of the 18th included in mesial angulation. Root apex of 17th indicates contiguity relations with the maxillary sinus floor where reactive mucus thickenings are valued. Dysodontiasis of the 28th. Reabsorption signs of the alveolar crest more marked at the 18th,17th,27th and 28th sites. Regular lingual vestibular thickness. No presence of periapical bone resorption.
            Lower dental arch: The alveolar crest and the lingual vestibular thickness in normal range limits. A periapical bone resorption small area with sharp margins in correspondence to the 35th.
Hospitalization at the II neurogical clinic of the San Martino Hospital in Genoa to take a sample of liquor. Discharge diagnosis: 1st and 2nd Motor Neuron Disease. Post-traumatic SAH (subaracnoid hemorrhage) due to an accidental fall in the ward.
At a general objective examination:
PA: 140/80; FC: 80 b/min R. No alterations on various organs and apparatus.
At the objective neurologic examination:
the patient is watchful, oriented in time, space and person, he shows collaboration. Lingual hypotrophy with bilateral fasciculations; neither dysphagia nor dyspnea. Important rhinolalia. At the upper extremities: no motor function test proximal to the maintaining of Mingazzini’s position: F=4 bilateral on the biceps and 3 ½ on the triceps. F=3 ½ bilateral on the extensor and flexor retinaculums of the wrist. First bilateral interosseous athrophy with referred muscle hypotrophy of the forearms. Hint of claw-hand deformity on both sides. Hyperactive deep tendon reflexes DTR’s. At the lower extremities: Mingazzini negative. At the segmental strength test, hyposthenia of the bilateral muscular rector femoris with F=4 ½ is present. Distad no strength deficit; mallet finger on the right side. Lively DTR at the 4 limbs with polycinetic patellas. Clonus of the lateral foot, unextinguishable on the left side. Bilateral extension of the big toe. No disturbs of the superficial sensitivity. Awkward coordination on the right at the forefinger-nose-chin test. Possible standing up.
Bio-humoral examinations in the range limits: Glycaemia, azotemia, creatine, uric acid, transaminase, LDH, CPK, GGT, alkaline phosphatase, calcium, phosphorus, magnesium, iron, total proteins, total bilirubin, total cholesterol, sodium, potassium, chlorine, amylasemia, blood count, PT, PTT, fibrinogen, serum protein electrophoresis and Bence Jone’s proteinuria, urine analysis, HbsAg, HIV 1/2 ab, HCV-Ab, total Treponema pallidum (Ab). Rheumatology tests: ESR, C-reactive protein, antistreptolisinico title (TAS), rheumatoid factors. FT3, FT4 and TSH.
Altered bio-humoral examinations:
Triglycerides 245 mg/dL (40 – 170).
Pandenoscopy Optics:
Laryngeal fibroscope: mobile true vocal cords, closure of the true vocal cords present in phonation, valid respiratory space, absence of salivary staunching. The sensitivity is present at a vallecula level but it is reduced. Deglutition tests have been performed in laryngeal fibroscope with: blue tinted water administered with a teaspoon: absence of residuals; water from the glass: it is fine if taken in small sips; it is fine to eat pudding with a teaspoon; processed cheese: staunching in the vallecula not perceived by the patient and removed partially by means of vain controlled deglutition; rusks: same as for processed cheese.
Therefore a diet with soft, not thready nor crumby food was recommended to be taken in small and well chewed boluses: liquids from glass taken in small sips; do not use the liquid to clean the food residues in the buccal cavity; after every three boluses make a vain deglutition; indications to administer the medicine orally are annexed here.
Simple spirometry: basal spirometry values within norm limits; diffusive values above norm.
Cerebral CT scan without contrast dated 08/09 (following an accidental fall in the ward): diffuse subarachnoid hematic shedding prevailing mainly in the left sylvian valley, in the upper and left suprasellar peritroncal cisterns. Front-basal bilateral hypodense contusions are not excluded. Tumefactions of the left tender occipital paramedian tissues. Median structures in axis. Ventricular system and subarachnoid spaces within the limits. Fracture line in the left occipital seat that reaches below the posterior profile of the homolateral occipital condyle.
Cerebral CT scan without control contrast on 08/11: the present control confirms the front-basal contusion hypodensities and a temporo-polar contusive hemorrhagic focus is appreciated on the left. Less represented is the subarachnoid hematic shedding. The remaining reports are unchanged.
Cerebral CT scan without control contrast dated 08/19: the greater part of the notorious hematic components has been reabsorbed. The front-basal bilateral hypodense notes are more recognizable, especially on the right; results.
Phoniatric assessment: phoniatric visit in patients with a suspect pathology of the 1st and 2nd motor neuron; at present absence of dysphasia; buccal cavity: symmetrical rima oris; tongue: presence of fascicular at rest that particularly involve the front two thirds of it, sensitivity present on all the area, mobile velum with maintained sensitivity.
Concerning the hospitalization in object, it has not been possible to proceed with the diagnostic rachiocentesis because the patient had an occipital trauma on 08/09 caused by an accidental fall without any loss of consciousness. Neuroradiology medical tests performed urgently have highlighted: fracture of the left occipital squama, diffuse left hematic contusion-hemorrhagic temporo-polar shedding with subarachnoid elements. Vascular malformations have been excluded through angio-CT studies. The following check-ups performed after 1 and 7 days have highlighted the complete reabsorption of the hematic components reported by the first CT scan.
Spirometry, phoniatric assessments were performed anyway with swallowing tests in fibro-laryngoscope and therapy with riluzole 50 mg 1 tablet at 8-21 hours was added. The patient will be contacted after 15-30 days to undergo a diagnostic rachiocentesis.

Expert's Opinion

The history and neurological examination findings are characteristic for motor neuron disease. The picture is one of amyotrophic lateral sclerosis (ALS) with combination of upper motor neuron and lower motor neuron abnormalities clearly documented. The atrophy and fasciculations in the tongue and weakness of the soft palate, some difficulty with swallowing, clearly show that the brainstem motor nuclei are affected in addition to the limb muscles. The MRIs of the brain and spine show changes in the upper motor neuron tracts, also characteristic for motor neuron disease and help exclude conditions that mimic ALS. The finding of the mild compression of the cervical spinal cord by disc and osteophytes is an incidental finding and not the cause of this neurological disorder.
The laboratory investigation is thorough and appropriate for the clinical syndrome and excludes alternative explanations for the motor neuron syndrome; this is then primary motor neuron disease of the ALS-type. I agree with the diagnosis of primary motor neuron disease of the ALS type.
The only other test relevant is EMG (electromyography> I am surprised this is not mentioned in the notes and may have been done. If not, this would be an important test to confirm the diagnosis. There is no need for lumbar puncture for CSF analysis.
Treatment, unfortunately, is for the symptom relief and supportive care only; Riluzole is appropriate and may prolong life by few months. There is no other proven treatment to stop, slow down or reverse this condition at this time. Anti-oxidant supplements such as combination B complex vitamins, vitamin E are often given but their value is unproven. Supportive therapy will improve survival and quality of life and is best provided by a multi-disciplinary team experienced in ALS; Respiratory care is or will be a critical component as well as maintenance of nutrition when swallowing becomes more difficult:  feeding gastrostomy, assisted ventilation are likely needed in the future.
Prognosis: Unfortunately, ALS is a very serious condition. Most people affected by this, live for about 12-18 months after diagnosis if good supportive care is given. This is especially so for respiratory care. There are rare cases with longer natural course for a few years; however the prominent affection of the brainstem functions with tongue and swallowing impairment indicate serious prognosis in this patient.
It is worth emphasizing that mental abilities remain normal in most people; decrease of cognitive function is rare. Pseudobulbar emotional ability can be improved with tricyclic antidepressant drugs such as amitriptyline.
Because supportive care improves quality of life and because this requires multidisciplinary care, referral to specialized neurology center is helpful.

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