As we all know that multiple sclerosis is a disease with a variable neurological deficit which relapses and remits and occurs in different part of the CNS. It will obviously have a wide differential diagnosis and will require a lot of clinical acumen to make a diagnosis. Let us look at a case report in a young man.
A 30-year-old Pathan male presented with decrease of visual acuity, intermittent diplopia, photophobia in both eyes and paresthesia of left hand. Family medical history was non-contributory.
Ocular and medical history of this patient included:
In June 2017, after an excessive food and alcohol intake, an acute diarrhea syndrome and vertigo occurred. After the treatment of the electrolytic imbalance, the patient was discharged. Fourteen days after this event, he presented in the Ophthalmology Clinic reporting decrease in visual acuity for 5 days, intermittent diplopia, photophobia, and vertigo.
Visual acuity was 0,12 in the right eye and 0,3 in the left eye. Intraocular pressure was 15 mmHg in both eyes. Slit lamp examination revealed segments of intrastromal rings in the right eye and a tight therapeutic contact lens in the left eye. Fundoscopic exam was normal. The optical coherence tomography (OCT) showed reduction of the retinal nerve fiber layer (RNFL) thickness in the inferior sector in both eyes.
The following entities are taken into account in establishing the differential diagnosis, when neurologic signs are present:
- Devic’s disease,
- infectious diseases (Lyme Borreliosis, hepatitis B, cytomegalovirus, and herpes simplex),
- toxic neuropathy,
- autoimmune disorders.
The cerebral MRI was done and supported the diagnosis of multiple sclerosis with ophthalmological onset.
Tests for other autoimmune disorders (pANCA, cANCA, total ANCA) and for Borreliosis need to be performed. The results were negative.
In cooperation with the neurologist, the treatment with intravenous (iv) corticosteroids (CS) was initiated: Methylprednisolone 500 mg/ day for 5 days, then 250 mg/ day for 2 days, followed by oral cortico-therapy.
Neuromyelitis optica spectrum disorders (NMOSD), are also known as Devic’s disease. They are inflammatory disorders of the CNS in which severe immune mediated demyelination and axonal damage targets the optic nerves and spinal cord. In this disease acute attacks of bilateral or rapidly sequential optic neuritis (leading to severe visual loss) or transverse myelitis (often causing limb weakness, sensory loss, and bladder dysfunction) with a typically relapsing course. Attacks most often occur over days, with variable degrees of recovery over weeks to months. Other suggestive symptoms include episodes of intractable nausea, vomiting, hiccups, excessive daytime somnolence or narcolepsy, reversible posterior leukoencephalopathy syndrome, neuroendocrine disorders, and (in children) seizures. While no clinical features are disease-specific, some are highly characteristic.
In some patients, optic neuritis and transverse myelitis occur concurrently; in others, clinical episodes are separated by a variable time delay. Relapse occurs within the first year following an initial event in 60 percent of patients and within three years in 90 percent. As a rule, severe residual deficits follow initial and subsequent attacks, leading to rapid development of disability due to blindness and paraplegia within five years.
The initial treatment is with high-dose intravenous methylprednisolone (1 gram daily for three to five consecutive days), in agreement with expert panel recommendations and based upon studies of multiple sclerosis and idiopathic optic neuritis.
Lyme disease is a tick-borne illness, which is typically caused by three pathogenic species of the spirochete Borreliella. B. burgdorferi is the primary cause of the disease in the United States. All three pathogenic species, B. burgdorferi, Borrelia afzelii, and Borrelia garinii, occur in Europe, and the latter two species have been identified in Asia.
Lyme disease has a broad spectrum of clinical manifestations, and it also varies in severity due, in part, to differences in the infecting species.
- Cutaneous manifestations are erythema migrans (EM). This may occur up to a month after the tick bite.
- Early disseminated disease is characterized by multiple EM lesions and/or neurologic and/or cardiac findings (that typically occur weeks to months after infection). Some of these patients have no history of antecedent early localized Lyme disease.
- Late Lyme disease is typically associated with intermittent or persistent arthritis involving one or a few large joints, especially the knee (sometimes preceded by migratory arthralgias), and/or certain rare neurologic problems, primarily a subtle encephalopathy or polyneuropathy. Late Lyme disease may develop months to a few years after the initial infection. Arthritis may be the presenting manifestation of the disease.
Other clinical manifestations are:
- Neck stiffness
- Regional lymphadenopathy
A variety of ocular manifestations have been associated with Lyme disease, including conjunctivitis, keratitis, iridocyclitis, retinal vasculitis, choroiditis, optic neuropathy, and uveitis. Papillitis is the usual manifestation.
What neurological manifestations are likely to be encountered?
Lymphocytic meningitis, unilateral or bilateral cranial nerve palsies (especially of the facial nerve), radiculopathy (Bannwarth syndrome), Peripheral neuropathy, mononeuropathy multiplex, cerebellar ataxia (rarely), encephalomyelitis (rarely)
The classic triad of acute neurologic abnormalities is meningitis, cranial neuropathy, and motor or sensory radiculoneuropathy, although each of these findings may occur alone.
Cardiac manifestations of Lyme disease include fluctuating degrees of atrioventricular heart block, sometimes with myopericarditis, which is usually mild when it occurs. On rare occasion, sudden cardiac death attributable to Lyme disease has also been reported. Chronic cardiomyopathy with heart failure has been linked to Lyme disease in Europe.
Diagnosis is based on several different ELISA tests of which the first one used is:
Whole cell-based enzyme linked immunosorbent assay (ELISA) – Whole cell-based ELISA tests are available for IgM (early), IgG (late), and combined IgM and IgG antibody detection. The combined preparation is typically used. This gives a 5% false positive test.
Western blot — The Western blot (or immunoblot) allows detection of antibodies to individual components of the organism and thus provides more information regarding which antigens of B. burgdorferi are reacting with serum antibodies than a whole cell-based ELISA. Separate Western blots are performed to detect either IgM or IgG antibodies.
PCR testing of specimens of CSF or synovial fluid for B. burgdorferi DNA in a reliable laboratory can add confirmatory information in seropositive patients. However, a positive PCR result by itself is likely to be a false-positive result, and a positive result does not prove that the patient has active infection, since spirochetal DNA may persist long after spirochetal killing has occurred.
B. burgdorferi has been isolated from skin biopsy specimens, blood, and CSFs. Two commonly used media are the modified Kelly-Pettenkofer and Barbour-Stoenner-Kelly II medium. Culture is not available in most clinical laboratories.
Other tests such as xenodiagnosis, T-Cell proliferation response and immune complex detection may be used.
Toxic and metabolic causes.
Toxic metabolic causes of optic neuropathy include an extensive list of possible agents. Typically, involvement is bilateral; onset may be abrupt or slowly progressive. The resulting loss of vision is usually permanent. the drugs involved are: carbon monoxide, ethylene glycol, methanol, perchloroethylene, tobacco, toluene, styrene. The antimicrobials which have been found to react with the optic nerve are: clioquinol, chloramphenicol, dapsone, ethambutol, isoniazid, iodochlorhydroxyquinoline, linezolid. Other drugs which are likely to affect the optic nerve are infliximab, patients treated with bevacizumab for glioblastoma, sildenafil and other drugs prescribed for erectile dysfunction. Amiodarone association with optic neuropathy remains somewhat controversial.
Systemic autoimmune disease
Optic neuritis is a rare manifestation of other systemic inflammatory or connective tissue disease and usually occurs in the setting of an established diagnosis
- Systemic lupus erythematosus (SLE). Optic nerve involvement occurs in approximately 1 percent of patients with SLE and may be due to vasculitis or to thrombosis secondary to antiphospholipid antibody syndrome
- Sjögren’s syndrome (SS). Optic neuritis may be the presenting symptom of this disorder.
- Granulomatosis with polyangiitis (Wegener granulomatosis). Extension of inflammation in the sinus and parasinus areas can produce optic neuritis, usually with other orbital signs.
- Behçet syndrome. Despite producing severe meningitis and uveitis, optic neuritis is a rare complication in this disorder.
- Inflammatory bowel disease. The higher than expected incidence of optic neuritis in these disorders may reflect coincidence of autoimmune diseases
Specific deficiencies of vitamins B12, B1, and folate have been implicated. Most nutritional optic neuropathies appear to be exacerbated by tobacco and possibly alcoholism (tobacco-alcohol amblyopia). Vision loss may be unilateral or bilateral, and can have an acute, subacute, or slowly progressive presentation. MRI is typically normal. Early vitamin supplementation and/or smoking cessation have been anecdotally associated with visual recovery, but this is not guaranteed.
Radiation-induced damage of the optic nerves and/or chiasm can occur 6 to 24 months after radiation therapy, usually for nasal carcinoma.
There are many reasons for a young man to lose his eyesight. Some of these causes are self evident i.e if he has received radiation therapy or an antimicrobial especially in tuberculosis. A good history needs to be taken and and a careful neurological examination needs to be done with a careful follow up upto a year. I have put down information which I hope you will find useful covered in one place. I have not been able to find a definite link to all the infections and optic neuritis. Perhaps you can do an extensive search and let me know.