Diagnostic pathway to amyotrophic lateral sclerosis (ALS): the significance of Babinski's sign in a unique patient and the necessity for a multidisciplinary approach

Abstract

In this case report, we present a patient with rare diagnosis of amyotrophic lateral sclerosis (ALS). In this patient, four different neurological disorders were diagnosed in a short-time period of 8 months. The first three diagnoses, chronic low back and leg pain, a left frontal gemistocytic astrocytoma WHO grade 2 and suspected Lyme's disease, could not fully explain the signs of physical examination. Finally, the diagnosis of ALS could reduce these signs to the same denominator.

Background

In this manuscript, we report about a patient who finally was diagnosed with amyotrophic lateral sclerosis (ALS) after an initial presentation of lumbago and leg pain. Two other diagnoses, a left frontal low-grade glioma and suspected neuroborreliosis, preceded this final diagnosis.

We present the clinical investigations and findings leading to the diagnosis of ALS.

This paper points out that a carefully taken history, a properly performed physical examination and interpretation, a critical approach to the imaging available and additional investigation for alternative diagnoses is very important in cases of complex diseases. Furthermore, the way to this diagnosis shows that interdepartmental, multidisciplinary cooperation is essential in the field of modern medicine.

Moreover, the remarkable history of this patient, who was diagnosed with lumbar stenosis, low-grade glioma and, finally, ALS, is unique.

Case presentation

A 64-year-old man with a history of more than 40 years of lumboischialgic complaints without other significant medical diagnoses was seen at the multidisciplinary neurosurgical/orthopaedic outpatient clinic after referral from the department of neurology of a general hospital.

The patient presented in April 2010 and has experienced since 4–5 months loss of control of the left leg with weakness in the entire left leg. These complaints increased after walking a few hundred metres after which he had to sit down and rest for partial recuperation. The patient did not complain of pain, sensory loss or sphincter disturbances.

At neurological examination, weakness of the left quadriceps, iliopsoas and the extensor hallucis longus muscle (MRC-grade 4) and a paresis (MRC-grade 3) of the dorsal flexors of the left foot was observed. There were no sensory disturbances of the legs. Furthermore, there was hyper-reflexia of both arms and legs with an indifferent plantar reflex of the right foot and a Babinski's sign of the left foot.

MRI scan of the lumbar spine was performed which showed a left-sided lateral recess stenosis at the level L4–L5 (figure 1).

Figure 1.

T2-weighted MRI scan of level L4-L5 showing a left lateral recess stenosis.

Since the pyramidal signs of the arms and legs, at neurological examination, were not explained by these MRI results, an MRI scan of the cervical and thoracic spine was performed along with electrophysiological analysis.

Additional MRI scans of the cervical and thoracic spine showed no abnormalities. Both motor-evoked and somatosensory-evoked potentials demonstrated a delay of central conduction times below the cervical level. Needle electromyography (EMG) did demonstrate spontaneous muscle fibre activity in the left paravertebral (L5) and left-leg muscles.

In May 2010, the patient was re-evaluated at the neurosurgical outpatient clinic with progression of the symptoms. The patient reported new complaints of paresis of the left arm. An MRI scan of the brain was performed the same day.

The MRI scan showed a diffuse left-frontal lesion, hypointense on the T1-weighted images, hyperintense on the T2-weighted images (figure 2) and no enhancement after Gadolinium administration.

Figure 2.

T2-weighted MRI scan showing a hyperintense lesion in the left-frontal lobe.

In June 2010, a tumour biopsy in the left frontal lobe was performed. Pathological examination established the diagnosis of a gemistocytic astrocytoma WHO grade 2 (figure 3).

Figure 3.

H&E staining shows increased cellularity due to proliferation of neoplastic astrocytes (×20).

Since the left-sided astrocytoma could not explain the predominantly left-sided pyramidal signs and the patient experienced a further neurological deterioration, the patient was referred to the neurological department. At that moment, the patient reported that he had experienced around eight episodes of acute weakness in both legs in the period between his 20th and 30th year.

Renewed neurological examination showed mild paresis of the left finger flexors, with otherwise normal strength of the upper extremities. A paresis grade 4 to 4+ was found in the leg abductors and foot flexors on both sides. In both the feet, gnostic sensibility was absent. Sense of vibration was lowered in ankles and knees. High reflexes were found on both the arms and the legs with an indifferent plantar reflex of the right foot, and a Babinski's sign of the left foot. The differential diagnosis at this time was (1) amyotrophic lateral sclerosis and (2) vacuolar myopathy in the course of hypokaliemic periodic paralysis. The latter possibility would, however, not explain the pyramidal signs. A second electromyography and a muscle biopsy were performed.

In August 2010, a second EMG demonstrated spontaneous and polyphasic muscle activity and fasciculations in the tibialis anterior muscle of both legs, in the gastrocnemius muscle of the left leg, and in the interossei, biceps and deltoid muscles of both arms. These results were also found in the right paravertebral muscles at the height of T6 and T10.

The biopsy demonstrated mild neurogenic muscle atrophy, but no evidence of vacuolar myopathy. No mutation of the CACNA1S gene was found.

The general practitioner of the patient performed a serological test for Lyme's borreliosis because the patient had reported a tick bite 7 months back. This test demonstrated positive IgM and a negative IgM and IgG after western blot analysis. Subsequently, a lumbar punction was performed. All tests for neuroborreliosis were negative in the cerebrospinal fluid and blood serum (Borrelia PCR, Borrelia IgG and IgM), eliminating the possibility of neuroborreliosis.

A third EMG was performed in November 2010, which demonstrated spontaneous and polyphasic muscle activity and fasciculations proximal and distal in both arms, distally, more than proximally, in both legs and in the right paravertebral muscles. These findings supported the diagnosis of probable amyotrophic lateral sclerosis.

Outcome and follow-up

In December 2010, the patient had a further decline in functioning. He was impaired in his activities of daily living due to progressive paresis of his hands and progressive spasms of his limbs together with difficulties with swallowing. After extensive consultation with his family and the general practitioner, he requested to have euthanasia. This decision was approved by an independent, certified doctor, according to Dutch law. Euthanasia was performed at the end of January 2011.

Discussion

In this case report, we present a patient with a unique combination of diagnoses. The history and the findings in this patient put the essence of the neurological examination forward.

The neurosurgeon and orthopaedic surgeon were consulted for a radiologically diagnosed stenosis of the lateral recess L4-5. The patient did not complain of pain or numbness in his leg, but he complained of loss of control in the leg. Also, hyper-reflexia of the legs and a Babinski's sign on the left side directed to a central neurological problem.

Owing to these findings, additional MRI scans of the spine and brain were performed and showed a left frontal lesion, which proved to be a gemistocytic astrocytoma. The astrocytoma in the left frontal lobe could, however, not explain the left-sided pyramidal signs.

The general practitioner started, based on the history and positive IgM in the serology, antibiotic therapy under suspicion of a (neuro)borreliosis after an earlier tick bite. Clinical manifestations of neuroborreliosis can be meningitis, meningoradiculitis, encephalopathy and peripheral neuropathy.¹ The clinical course of this patient could not be explained by neuroborreliosis; moreover, this was ruled out by examination of the cerebrospinal fluid.

Since amyotrophic lateral sclerosis was suspected, an EMG was performed. This showed abnormalities; however, the El Escorial criteria for motor neuron disease were not met.²

Vacuolar myopathy and associated muscle weakness can occur in the course of hypokaliemic periodic paralysis.³ Although the suspicion was low (hyper-reflexia is not to be expected in myopathies), a muscle biopsy was performed to rule out this possibility. This showed the absence of a mutation in the CACNA1S gene, for which hypokaliemic periodic paralysis was deemed more unlikely.³

Finally, with a third EMG, diagnosis-probable amyotrophic lateral sclerosis was made.

ALS or motor neuron disease is a fatal neurodegenerative disease. The incidence in Europe is estimated at 2.16/100 000 person-years. For sporadic disease, the peak age is 58–63; for familial disease, the peak age is 47–52 years.⁴ ALS is a disorder which affects the motor system in all levels, showing clinical signs of lower and upper motor neuron defect. Although ALS is defined as a motor neuron disease, sensory symptoms, as reported by this patient, are described.⁵ The disease is usually rapidly progressive; 50% of the patients die within 30 months of symptom onset; 20% will survive the first 5 till 10 years after symptom onset. ALS is a clinical diagnosis supported by electrophysiological criteria.²

Disease management consists mainly of symptomatic treatment aimed at maintenance of quality of life. In two randomised controlled trials, it is shown that riluzole, a glutamate release inhibitor, extends survival by 3–6 months.⁴

A cohort study from 2009, in The Netherlands, of 209 patients diagnosed with ALS showed that, between 2000 and 2005, 16.8% of these patients decided on euthanasia or physician-assisted suicide. The most common reasons mentioned to choose these end-of-life practices were fear of choking, no chance of improvement, loss of dignity, being dependent on others and fatigue.

Euthanasia is legalised by Dutch law with the Euthanasia Act of 2002. The physician who performs euthanasia will not be prosecuted as long as the whole process is in line with the criteria described in that act. These criteria include that the patient must have insight in his terminal disease; the will of the patient to die is voluntary and carefully considered; the patient is experiencing unbearable suffering and there are no realistic alternatives for a treatment. Also a second, independent, physician has to approve the procedure leading to euthanasia.⁶

Learning points.

• A critical approach and interpretation of imaging is essential in the field of neurology and neurosurgery.

• A proper neurological examination, in patients with back pain, should always be performed to rule out neurological pathology.

• It is of great importance to pursue close cooperation between departments and different medical disciplines in order to obtain a diagnosis in complex cases.