Acute visual loss


Optic neuritis (ON) is the most common acute optic neuropathy below the age of 45. The annual incidence is about 1 per 100,000 in low risk populations. It presents typically as a progressive painful loss of vision (worse with eye movements) in young adults that recovers greatly over months. In the acute phase, findings include visual field defects (central or paracentral vision loss or altitudinal defects), afferent pupillary defect, disproportionate loss of color vision (red desaturation), a reduced visual acuity, abnormal VEPs. In up to 60% the optic disc may be normal (retrobulbar neuritis). When there is swelling of the optic disk the term papillitis is used. Optic neuritis can be unilateral or bilateral. Unilateral ON is very often reversible often seen under the age of 40. Following resolution, in practically all patients subtle residual defects may persist such as defective color vision, depth perception, and contrast sensitivity. In bilateral ON there is often lack of pain, there may be anterior uveitis. ON progresses over the first two weeks and then improves progressively. A work-up to exclude MS should be performed particularly in patients with unilateral ON. The likelihood of developing definite MS within 3-5 years following an episode of ON and abnormal MRI ranges between 40 to 80%. This contrast with only 10% in patients with normal MRI.


Toxic and nutritional optic neuropathy: Toxic (methanol, ethyl alcohol, ethambutol, amiodarone, clioquinol, chemotherapeutic agents ethylene glycol, tobacco) and nutritional (vitamin B1 and B12 deficiency) optic neuritis present with cecocentral scotoma.  Radiation-induced optic neuropathy


Leber hereditary optic neuropathy (LHON): These comprise a group of disorders presenting with cecocentral scotoma, negative imaging and a positive family history. Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder usually affecting men between the age of 15-35 years and presents with acute or subacute painless visual loss in one eye, the next eye following weeks or months later. Progressive cerebellar ataxia, hyperreflexia, peripheral neuropathy and cardiac conduction abnormalities are also common findings. Fluorescein angiography may help distinguishing the LHON optic disc from true disc edema. ERG, and CSF are normal. Dystonia may occur which may be accompanied by the presence of striatal lesions on MRI. The work up will require a blood sample for mitochondrial DNA analysis may include primary mutations at T3394C, G3460A, A4136G, T4160C, T14484C or G11778A, the latter having the worst prognosis. Asymptomatic maternal relatives have abnormal fundi. Early onset ataxia with optic atrophy are a heterogeneous group of disorders which can occur in combination with Friedreich ataxia, X-linked ataxia, leucodystrophies ALD, KLD, sialidosis, MELAS, biotin deficiency or demyelinating disease. CPEO, MNGIE, NARP and Kearns-Sayre syndrome are two other mitochondrial disorders associated with optic neuritis.


Vascular optic neuropathy: Vascular forms of ON include arteritic (autoimmune disease) and non-arteritic anterior ischemic optic neuropathy (AION). The latter is the most common cause ON in the elderly and presents as a sudden (most often unilateral, 40% bilateral) painless loss of vision. Vascular risk factors in patients suffering from AION include hypertension, diabetes and smoking. In contrast to ON recovery is uncommon, less than 50% of patients show improvement in visual acuity 6 months after the event. GCA with or without disc swelling is another cause of ON in the elderly and should be considered as a neurological emergency. Uncommon forms of vascular ON include central retinal vein occlusion, aneurysms, arteriovenous malformations and carotid-cavernous fistula. Other vascular causes include: Giant cell arteritis, microangiopathy of the brain, retina, and inner ear (Susac syndrome), acute posterior multifocal placoid pigment epitheliopathy, Eale disease (noninflammatory occlusive disease of the retinal vasculature), Cogan syndrome (interstitial keratitis, vestibular dysfunction, and deafness) and systemic hypercoaguable states, including anticardiolipin syndrome.

Central retinal vein occlusion is usually characteristic on funduscopy: flame shaped hemorrhages within the distribution of the affected vein. The patient may complain of a sudden painless unilateral loss of vision or visual field (for example, inferior field defects for superior branch retinal vein occlusion) or may be asymptomatic. If loss of vision is severe a RAPD may exist, indicating retinal ischemia. Important systemic risk factors for retinal vein occlusion include hypertension, diabetes mellitus, and other conditions such as hyperhomocystinemia. Glaucoma is an important ocular risk factor.

Patients with retinal telangiectasia may present with retinopathy. In younger patients this is referred to as Coats disease. It usually occurs in young men aged less than 20 years and is associated with FSHMD, high-frequency sensorineural hearing loss, and detachment.

Retinopathy in non-diabetic patients include retinal vein occlusions, retinal telangiectasia, and retinal macroaneurysms. Common systemic causes include systemic hypertension, carotid atherosclerotic diseases, blood dyscrasias, systemic infections, and past radiotherapy.


Infectious optic neuropathy: These can occur at any age but is more likely to occur in immunodepressed patients. Infectious neuropathy with or without encephalitis, post and paraviral infections, herpes zoster, infectious mononucleosis and syphilis are the most common ones. Cat-scratch fever causes a typical neuroretinitis which needs to be differentiated from all other forms of optic neuropathy: MS, Behçet disease, hypertensive retinopathy, ischemic optic neuropathy, CNS vasculitis and viral meningitis.


Inflammatory and infiltrative optic neuropathy: These can be caused by compressive (meningioma, metastasis, hemangioma, lymphangioma, thyroid orbitopathy), infiltrative (glioma, glioblastoma, leukemia, lymphoma, carcinomatous meningitis) or inflammatory (sarcoidosis) lesions. Neuroimaging helps to differentiate these forms from other forms of ON.


Paraneoplastic optic neuropathy: These include cancer-associated retinopathy, cancer-associated cone dysfunction, melanoma-associated retinopathy, diffuse uveal melanocytic proliferation and paraneoplastic ganglion cell neuronopathy.


Intracranial hypertension: Cerebral venous thrombosis, meningitis, hydrocephalus, intracranial mass lesion, encephalopathies, IICHT.


Traumatic optic neuritis: May occur with little or no evidence of head trauma.


Exudative optic neuritis: Central serous chorioretinopathy and optic disc drusen


Occipital lobe seizures (ictal blindness): Bilateral loss of vision, together with fluctuation in the patient’s level of alertness, as well as the episodic conjugate deviation of the eyes vertical or lateral, along with jerky eye movements, may suggest seizures. Other symptoms include elementary visual sensations (aura) such as white or colored flashing lights, often in the part of the visual field corresponding to the focus. Fading, blurring, or loss of part of all of vision may occur at the start of the occipital seizure. Scotoma, hemianopia or amaurosis may also occur; these symptoms may be isolated to one portion of the visual field, or may spread. EEG confirms and demonstrates the epileptic focus originating in the left occipital area, that produces focal status epilepticus and intermittent non-convulsive generalization. The etiology is often unknown, the remainder have tumoral epileptogenic lesions, history of severe head trauma, vascular lesions (with calcifications often associated with celiac disease), RPLE, birth injury, cortical dysplasia and heterotopia, history of meningitis or encephalitis, pial angiomatosis, and porencephalic lesions; a few may have unrecognized MELAS syndrome.


Subacute necrotizing encephalopathy (SNE) or Leigh disease: Several synonyms exist such as Leigh necrotizing encephalopathy, subacute necrotizing encephalopathy, Leigh syndrome and necrotizing, encephalomyelopathy of Leigh. Adult-onset forms of SNE are sporadic, or inherited in an autosomal recessive, autosomal dominant, X-linked, or mitochondrial trait. To complicate matters even more several different types of genetically determined enzyme defects can cause SNE. As with other mitochondrial disorders, the onset of neurologic symptoms present from the 1st to 6th decade with acute or subacute onset, often precipitated by surgical intervention or febrile illness. The disease can present with a variety of symptoms such as brainstem dysfunction (central respiratory failure, intermittent oculomotor palsy, cranial nerve dysfunction including deafness, optic atrophy or Wernicke-like syndrome), ataxia, or extrapyramidal (dystonia) symptoms, global cognitive (dementia or mental retardation 30% of patients), spastic paresis, myoclonic jerks and seizures, peripheral demyelinating polyneuropathy, motor decline and unconsciousness with lactic acidosis. In addition, insulin-resistant diabetes mellitus, muscular weakness, intractable nausea and vomiting, and anemia can occur. The disease can be intermittent progressive or remitting/relapsing. CSF protein may be increased. Brain MRI shows abnormal high intensities in basal ganglia, particularly putamen, on T2 weighted images, bilateral medial regions of the thalamus, brainstem and periaqueductal gray matters. Proton MRS may show elevated lactate level in involved regions of the brain. Ragged red fibers can be found on muscle biopsy with increased succinic dehydrogenase activity and cytochrome oxidase negative fibers in almost 90% of cases. Pre- and postprandial serum and CSF lactate and pyruvate are useful in the diagnosis. Serum lactate is increased in 50% of patients but is less sensitive than CSF lactate. Pyruvate dehydrogenase deficiency (or Lactic and Pyruvate Acidemia with Episodic Ataxia and Weakness) presents with episodic ataxia, seizures, and hypoglycemic episodes and may mimic SNE. Serum and urine amino acid analyses reveal hyperalaninemia. Treatment for SNE is empirical but the administration of thiamine, vitamin B1, Coenzyme Q10 have been used. The prognosis is usually bad with survival rates less than a few years after onset.


Subacute sclerosing panencephalitis (SSPE): SSPE is a neurodegenerative disease due to persistent measles (rubeola) infection that affects children and young adults. Onset of the disease is insidious (incubation time 6-8 years) and often only recognized after significant neurologic deficits occur. The diagnosis of SSPE can be made if three of the following five criteria are fulfilled: 1) typical clinical presentation with progressive cognitive decline and stereotypical myoclonus (sustained myoclonus e.g. truncal myoclonus, limb extension associated with tongue protrusion and momentary speech arrest followed by loss of tone in all total lasting  seconds), 2) characteristic EEG changes, 3) elevated CSF IgG levels without pleocytosis, 4) elevated CSF measles antibody titers, and 5) typical histopathologic findings in a brain biopsy or autopsy. Affected individuals progress through four loosely defined clinical stages at differing rates. Stage I is characterized by subtle behavioral changes, cognitive decline, emotional lability, lethargy, and nonspecific neurologic symptoms. This stage may last for weeks to months. Stage II includes continued intellectual decline, myoclonus, focal seizures with secondary generalization, choreoathetosis, apraxia, and visual changes with optic atrophy, dysarthria, and tremors. A wide variety of visual disorders have been associated with SSPE, including papilledema, (chorio)retinitis, optic nerve pallor, homonymous visual field deficits, and cortical blindness. This stage may last three months or less. Neurologic decline persists in stage III (decreased level of consciousness, autonomic instability (with a variable heart rate and widely fluctuating temperatures and blood pressures), dystonia and rigidity, decorticate/decerebrate posturing), but the pace slows down, and symptoms may stabilize for one to two years. Features of stage IV include active startle reflex, flexor limb positioning, quadraparesis, akinetic mutism, wandering eye movements and coma. At this time, myoclonus, seizures, and rigidity are less frequent than in prior stages. CSF reveals markedly elevated intrathecal IgG synthesis rate and multiple oligoclonal bands on high-resolution electrophoresis, without a cellular reaction. Serum and CSF measles IgG titers are elevated with normal IgM titers. The EEG exhibits periodic complexes with generalized bilateral, usually synchronous and symmetrical sharp and slow wave complexes of high amplitude (greater than 500 uV), classically occurring every 5-10 seconds. Early in the course of the disease these periodic discharges may occur on a normal background but later the background becomes increasingly slower and disrupted. These periodic complexes are usually associated with clinically evident myoclonic or dystonic activity. MRI may be normal or may show early changes of increased signal on T2-weighted sequences, frequently involving the periventricular or subcortical white matter in the frontal, temporal, and occipital white matter; late changes include significant white matter loss, approximately 30% of patients show basal ganglia changes, while 25% have cortical changes. Fifty percent of patients who develop SSPE had measles before two years of age, and 80% before age four years. Five percent of patients survive three months or less and 20% survive four or more years, with a mean survival of only 18 months. Death occurs in stage IV, often the result of intercurrent illnesses such as pneumonia. MS (visual changes, oligoclonal bands) is often considered in the differential diagnosis of SSPE. Treatment is disappointing. The most promising results to date have used a combination of inosiplex, an antiviral agent, and intraventricular or intrathecal alpha-interferon as an immunomodulator, with stabilization or improvement in some patients. If successful CSF titer of measles antibodies should decrease over the months to come. Early childhood measles vaccinations remain critical in limiting the incidence of SSPE.


Chronic visual loss



Gyrate atrophy of the choroid and retina with hyperornithinaemia (GACRH): This autosomal recessive disorder is caused by inherited deficiency of ornithine-delta-aminotransferase activity (chromosome 10) leading to high ornithine concentrations in body fluids. It is clinically characterized by a triad of progressive constriction of the visual fields leading to blindness by middle age, early cataract formation, and type II skeletal muscle fiber atrophy. Brain MRI revealed degenerative lesions in the white matter in 50% of the GA patients, and 70% of the patients had premature atrophic changes, with a striking increase in the number of Virchow spaces. Creatine is depleted in muscle and brain. Measurement of plasma and urine amino acids provides the diagnosis. SEP and BEAP may be abnormal.


Sialidosis II: Type II sialidosis is the severe form of the disease, which can be subdivided into three forms: (I) congenital or hydropic (in utero), (II) infantile (0-12 months), and (III) juvenile (2-20 years). The juvenile form is often a combined deficiency of neuraminidase and β-galactosidase (galactosialidosis). It is characterized by the same visual characteristics as sialidosis type I. All type II patients eventually develop progressive mucopolysaccharidosis-like features, including coarse facies, visceromegaly, dysostosis multiplex, vertebral deformities and severe mental retardation. Sialidosis is inherited as an autosomal recessive genetic trait.


X-linked adrenomyeloneuropathy (X-AMN): The adult form of this X-linked recessive peroxisomal disorder starts on average at the age of 28 years and is predominantly confined to the spinal cord (adrenomyeloneuropathy). Cerebral involvement is observed in half of the cases. X-AMN is often misdiagnosed as “familial MS”. Slowly progressive spastic paraparesis with sensory deficit (predominantly reduced vibratory sensation), bladder dysfunction and mild distal mixed axonal demyelinating polyneuropathy are common features. These clinical symptoms are often preceded or followed by behavioral disturbances or frontal dementia (mania, psychosis and cognitive impairment) and are often misdiagnosed as brain tumor. Both neuroleptic and anticholinergic medications may result in significant side effects with little resolution of the underlying psychiatric symptoms. Adrenal insufficiency (Addison syndrome) develops in 70% of the patients before, during or after the onset of the neurological syndrome, and does not correlate with the severity of the neurological disease. 20% of heterozygous female patients may develop a late middle age syndrome, which resembles adrenomyeloneuropathy (spastic paraparesis, loss of vibration, long tract signs and peripheral neuropathy), but are unlikely to develop adrenal dysfunction. Other phenotypes are pure adrenal insufficiency or simply asymptomatic carriers. The diagnosis is confirmed by the presence of increased levels of saturated VLCFA in plasma (15% false negative in female heterozygotes) and cultured skin fibroblasts or white blood cells. CSF reveals increased intrathecal IgG. NCVs in patients with X-AMN are often abnormal and suggest a mixture of axonal loss and multifocal demyelination. Although MRI can be normal in up to 50% of patients, high signal intensities in the periventricular parieto-occiptal white matter (often asymmetric and mimicking brain tumor) have been reported in cerebral forms. However in 15% the initial lesions may be frontal. MRI findings may often provide the first clue to the diagnosis. A decreased N-acetylaspartate/choline ratio is found on MR spectroscopy. BAEP reveals prolonged latencies of III-V. The defective ALDP gene encodes for ATP-binding cassette transporter involved in transport of VLCFA into peroxisomes and has been mapped to Xq28.


Krabbe leukodystrophy (KLD): Three adult forms of this slowly progressive autosomal recessive disorder have been reported: (1) familial spastic paraplegia or tetraplegia, (2) an asymmetric pyramidal syndrome and (3) an asymptomatic form. Later on features such as frontal dementia, seizures, cerebellar ataxia, optic atrophy and demyelinating sensorimotor peripheral polyneuropathy appear. Motor nerve conduction is substantially reduced (NCVs may however be normal). CSF protein levels may be normal. MRI may be normal but most often reveals increased signal intensity on T2 in the spinal pyramidal tracts, bilateral in the white matter of the cerebrum and brainstem. Proton MR spectroscopy shows increased choline and myoinositol in affected white matter. The diagnosis is based on the presence of low lysosomal galactocerebrosidase activity (<5% of normal) in white blood cells or cultured dermal fibroblasts. Some healthy individuals may have low enzyme activity. The gene maps to 14q25-31.


Mitochondrial encephalopathy lactatic acidosis syndrome (MELAS): The frequency of MELAS in the adult population averages 16/100,000. The disorder can onset in adulthood and may remain unrecognized until precipitated by metabolic stress. Epileptic seizures (particularly partial seizures, photoparoxysmal EEG responses and focal or multifocal EEG epileptiform activities) are the first recognized symptom in adults and can occur at any age. In contrast to KSS, MELAS and MERRF are often familial. Mitochondrial DNA is transmitted only from females to their offspring but a single female can bear offspring who harbors different levels of mutant mitochondrial DNA and have a variable phenotype. Clinical features are short stature (with normal milestones), sensorineural hearing impairment in late childhood (clinically obvious in 94%), exercise intolerance, in 4th and 5th decades diabetes mellitus (or impaired glucose intolerance), migraine-like headaches, epilepsy, recurrent stroke-like episodes commonly involving the posterior part of the cerebrum (occipital brain infarct resulting in hemianopia/cortical blindness)(10% of occipital strokes between the age of 18- 45 years are due to MELAS), ophthalmoplegia, retinal pigmentary abnormalities (usually asymptomatic and best detected by retinal photography), cerebral white-matter disease, basal ganglia calcifications (54%), hypertrophic cardiomyopathy, syncopal attacks due to complete atrioventricular block, neuropathy (predominately axonal form), dementia or psychiatric manifestations or ataxia. The diagnosis of a mitochondrial myopathy can be confirmed by increased CSF lactate level, muscle biopsy (enzymatical assay) and molecular-genetic investigations on muscle specimen (in 80% of patients mtDNA point mutation at A3243G in the tRNA gene of mt DNA). MtDNA analysis on hair follicles is as sensitive as muscle in detecting this mutation. Analysis using blood samples appears not as sensitive, particularly in older subjects. Diffusion weighted MR findings support the metabolic rather than the ischemic pathophysiological hypothesis for stroke-like episodes occurring in MELAS. Normal or increased apparent diffusion coefficient values within 48 hours of a neurological deficit of abrupt onset should raise the possibility of MELAS, especially if conventional MR images show infarct-like lesions (cortico-subcortical posterior temporal and parieto-occipital). Brain MRI reveals leukoencephalopathy. Regional cerebral blood flow (rCBF) in patients with MELAS, using [123I]N-isopropyl-p-iodoamphetamine or 99mTc-hexamethyl propyleneamine oxime SPECT shows focal hypoperfusion in the parietal and/or occipital lobes. In vivo lactate determination in brain by 1H NMR spectroscopy can be helpful in evaluating prognosis. Early death (cardiopulmonary failure, status epilepticus and pulmonary embolism) has been reported in MELAS (mean age of 34 years). Hypertrophic cardiomyopathy advancing to dilated cardiomyopathy. There is evidence for maternal inheritance, and the mutation is always present in oligosymptomatic maternal relatives and most asymptomatic maternal relatives. The encephalopathy is often mistaken for herpes encephalitis and CADASIL.


Leber hereditary optic neuropathy (LHON): These comprise a group of disorders presenting with cecocentral scotoma, negative imaging and a positive family history. Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder usually affecting men between the age of 15-35 years and presents with acute or subacute painless visual loss in one eye, the next eye following weeks or months later. Progressive cerebellar ataxia, hyperreflexia, peripheral neuropathy and cardiac conduction abnormalities are also common findings. Fluorescein angiography may help distinguishing the LHON optic disc from true disc edema. ERG, and CSF are normal. Dystonia may occur which may be accompanied by the presence of striatal lesions on MRI. The work up will require a blood sample for mitochondrial DNA analysis may include primary mutations at T3394C, G3460A, A4136G, T4160C, T14484C or G11778A, the latter having the worst prognosis. Asymptomatic maternal relatives have abnormal fundi. Early onset ataxia with optic atrophy are a heterogeneous group of disorders which can occur in combination with Friedreich ataxia, X-linked ataxia, leucodystrophies ALD, KLD, sialidosis, MELAS, biotin deficiency or demyelinating disease. CPEO, MNGIE, NARP and Kearns-Sayre syndrome are two other mitochondrial disorders associated with optic neuritis.


Spinocerebellar ataxia:

SCA-1: SCA-1 maps to chromosome 6p22-p23 (ataxin-1). The prevalence of SCA-1 is about 3-15% among ADCAs. Its onset is in the 2nd and 3rd decades. Ataxia is an early and prominent feature along with optic atrophy, dysphagia and pyramidal signs with prominent spasticity. Atrophy and fasciculations may occur late in the facial, lingual and mastication muscles. Loss of vibration, progressive extrapyramidal features and ophthalmoplegia (slow saccades) occur less frequently and are often late manifestations. Axonal sensory or sensorimotor polyneuropathy is found in 42% of patients. There may be some intellectual decline. MRI shows cerebellar and pontine atrophy. CSF is normal.

SCA-7: This autosomal dominant disorder typically presents with progressive ataxia, upper motor neuron signs (brisk reflexes), macular or retinal degeneration with visual loss, and slow saccades. They often start in childhood. SCA-7 is mapped to chromosome 3p14.1-p21.1. Early onset cases may present with dementia. This form is often misdiagnosed as MS. SCA-7 constitutes about 5% of ADCAs.


Friedreich ataxia (FA): This form of ataxia is the most common hereditary form (autosomal recessive with variable phenotype) with a frequency of 1/50,000 in the population. Essential diagnostic criteria include its onset before the age of 25 years and <5 years after onset the development of the following: progressive gait ataxia, early areflexia in lower limbs, vibration and joint position sensory deficits, extensor plantar responses, and motor nerve conduction velocity >40 m/s in upper limbs with small or absent SNAPs consistent with axonal sensory neuropathy. Other features are scoliosis, club feet, cardiomyopathy (>50%), diabetes or impaired glucose tolerance (10%) and dementia. Optic neuropathy and deafness occurs in less than 25% of cases. Life expectancy of FA is on average 35 years, death occurring from heart failure. The locus is mapped to chromosome 9q13-q21.1 (frataxin). Frataxin results in intramitochondrial iron accumulation, which explains why FA is now considered a mitochondrial disorder. Abnormal ECG and echocardiography are seen in approximately 60% of cases. CSF is normal. The condition most frequently confused with FA is HSMN I. This demyelinating form of HSMN, is essentially characterized by autosomal dominant inheritance with slow conduction velocities (always <40 m/s). Late-onset FA (after the age of 25 years) (LOFA) is characterized with a slower progression and lower incidence of skeletal deformity. Investigations should include brain MRI, serum vitamin E and B12 levels, and a-fetoprotein levels and DNA analysis to detect GAA trinucleotide expansion.


Kufs disease (adult neuronal ceroid lipofuscinosis): In adolescence to middle age adulthood, two clinical Kufs phenotypes emerge; type A, featuring progressive myoclonic epilepsy with marked photosensitive and generalized tonic-clonic seizures developing at around the age of 30 years with subsequent ataxia, and dysarthria, dementia, and later pyramidal and extrapyramidal signs. There are no visual problems and seizures are often refractory; and type B, dominated by neuropsychiatric symptoms, including behavioral disturbances and dementia, and may be associated with cerebellar or extrapyramidal signs (cranial dystonia including facial dyskinesias or parkinsonism). The dementia syndrome is characterized by gradual onset, progressive course, and deficits in episodic memory, executive function, and visuospatial abilities; these features and the pattern of cognitive dysfunction thus overlap those of more common neurodegenerative dementing illnesses, including AD. Dementia may be the presenting symptom of Kufs disease and may not be manifested until the seventh decade of life. Unlike other forms of neuronal ceroid-lipofuscinosis, it does not cause blindness. Electrophysiologic and neuroradiologic studies are nonspecific. Giant VEP and large SSEPs can be elicited. Abnormal photic drive (high-amplitude spike at low rates of stimulation) is observed during EEG. Brain MRI may show predominantly cerebellar atrophy and signal changes on T2 in the putamina. The diagnosis is based on the presence of granular osmiophilic deposits found by EM in rectal, muscle, skin or liver biopsy and are deficient in lysosomal palmitoyl protein thioesterase. Urinary sediment dolichol levels are elevated in both types. The disease is autosomal recessive (rarely dominant) and caused by mutation in CLN3 gene of which the locus is unknown. Kufs disease should be considered when seizures and motor disturbances complicate the early course of atypical dementia in middle adult life. Visual loss and optic atrophy are unusual and in combination with the later age at onset clinically distinguished Kufs disease from other NCLs. Mean length of illness is about 7 years.