fashion, the pupil near response is restored, but the pupil light reflex remains absent or dysfunctional. Thus, the peripheral form of LND is due to aberrant regeneration bringing restoration of the near reflex whereas central LND is due dorsal midbrain injury impairing the light reflex while sparing the near reflex.

The clinical scenario: Bilaterally small pupils with light-near dissociation

The look-alikes: Chronic Adie’s pupils vs. Argyll Robertson pupils

Tip: In a patient with pupillary light-near dissociation, slow and sustained contraction of the sphincter during and after near effort is characteristic of an Adie’s pupil.

Convergence spasm vs. bilateral sixth nerve palsies

Case: A 23-year-old girl was referred because of a two-week history of diplopia, frontal headaches and blurred vision. Her diplopia was horizontal and intermittent, worse at distance than at near, and

present in all fields of gaze. She was taking no medications and there was no history of trauma. Visual acuity was 20/100 at distance in each eye. Confrontation visual fields and fundus appearance were normal and there was no ptosis or proptosis. She was esotropic in primary position but the angle of esodeviation varied during cross-cover testing. There was moderate limitation of abduction in both eyes that was also variable (Figure 9.7). The remainder of her neurologic examination was normal. Bilateral sixth nerve palsy was diagnosed and the patient was referred for immediate neuroimaging.

While the presence of esotropia and abduction deficits suggests a diagnosis of bilateral sixth nerve palsy, the marked variability of her abduction deficit raised the possibility of myasthenia or convergence spasm.

What clinical findings would support a diagnosis of convergence spasm?

The key to making this diagnosis, also termed spasm of the near reflex, is the presence of other components of the near triad during periods of ocular misalignment. This is usually demonstrated by

A

B

Figure 9.8 The same patient seen during an episode of esotropia (A) and between episodes when the eyes were aligned (B). Note that pupillary constriction accompanies the esotropia.

observing constriction of the pupils during episodes of esotropia. Closer examination in this patient did reveal marked miosis during periods of esotropia (Figure 9.8). Further history disclosed that her symptoms began shortly after the unexpected death of a family member. She was reassured as to the benign nature of this condition and six months later her examination was completely normal.

In addition to pupillary constriction during episodes of esotropia, excessive contraction of the ciliary body is also present, accounting for blurred vision at distance in this syndrome. The degree of

such accommodative spasm depends in large part on the age of the patient. In children and young adults, the resultant pseudomyopia, demonstrated by a disparity between the manifest and cycloplegic refractions, can be quite large.

Another helpful examination technique for identifying convergence spasm is comparison of ocular motility with binocular vs. monocular viewing. Tested with both eyes open, the patient with convergence spasm demonstrates variable esotropia and an apparent (usually bilateral) abduction deficit. When one eye is patched, the same patient will often demonstrate a strikingly normal range of abduction (Figure 9.9). In addition, there is often a disparity between eye movements when tested formally (refixation saccades and pursuit movements) versus performed during random eye movements. When convergence spasm is suspected, one should observe the patient’s ocular motility while conversing or while performing other tasks.

Discussion: The near reflex is a normal synkinesis of convergence, accommodation and pupillary constriction that serves to keep a near target in focus on the fovea. Spasm of the near reflex occurs when this reflex is inappropriate for the visual task, i.e. invoked during distance fixation or excessively strong for a near target. Such spasm of the near reflex may occur as discrete episodes or, less commonly, as sustained activation of these three components. Symptoms include blurred vision, diplopia and brow ache. When convergence spasm is the prominent feature, episodic and variable esotropia may be mistaken for ocular myasthenia, but the

observation of miosis and/or pseudomyopia should distinguish spasm of the near reflex. Some patients also exhibit other excessive facial movements such as squinting, blinking or grimacing during episodes of esotropia. When convergence spasm is more sustained, persistent esotropia may be attributed to unilateral or bilateral sixth nerve palsy. Sixth nerve palsy is characterized by esotropia that worsens in lateral gaze and is greater at distance than near and, importantly, slowing of abduction saccades.

Unlike many brainstem reflexes which are unconscious and involuntary, the near reflex can be activated voluntarily. The large majority of cases of convergence spasm are functional in nature, i.e. non-organic. Rarely, spasm of the near reflex is due to organic disease and in such cases other neurologic abnormalities are typically present. These organic causes of convergence spasm include midbrain disorders (stroke, encephalitis and tumors), metabolic derangements (Wernicke’s encephalopathy, phenytoin toxicity) and Chiari I malformation. Head trauma occasionally produces sustained accommodative spasm. In a neurologically intact patient with isolated, episodic convergence spasm, neuro-imaging is unnecessary. In patients with a history of head trauma, persistent spasm or other neurologic deficits, neuro-imaging and metabolic evaluation is recommended.

In the absence of an organic cause, management of patients with spasm of the near reflex is generally symptomatic. Diverse strategies are used but none with great success. Sources of stress and anxiety can often be identified and, ideally, corrected. Relax-

ation exercises such as meditation and yoga may be of some benefit. A variety of anxiolytic agents and muscle relaxants have been employed with varying results. It is sometimes tempting to prescribe refractive correction for the induced myopia, but this can be problematic because the patient is then required to maintain vigorous accommodation in order to see clearly. Alternatively, accommodative spasm can be blocked with a trial of topical cycloplegics, but the patient will then need reading glasses for near tasks. Furnishing base-out prism for convergence spasm is rarely helpful since the degree of esotropia is so variable.

The clinical scenario: Acute esotropia with bilateral abduction deficits

The look-alikes: Bilateral sixth nerve palsies vs. convergence spasm

Tip: Esotropia due to convergence spasm is accompanied by miosis.

Wernicke’s encephalopathy vs. brainstem stroke

Case: A 39-year-old real estate agent was in the first trimester of her first pregnancy when she awoke with diplopia. She had not been well for several days, feeling lethargic, off-balance and slightly disoriented; symptoms that she attributed to severe morning sickness during the previous eight weeks. She was not taking any medications and had been

previously healthy. Examination revealed bilateral ptosis, limitation of gaze in all directions, slow upward saccades, upbeat nystagmus and mild ataxia (Figure 9.10). On cross-cover testing there was a small right hyperphoria. She was suspected of having suffered a brainstem stroke due to a pregnancyrelated hypercoagulable state.

What aspect of this case makes an acute brainstem stroke unlikely?

This patient exhibits both horizontal and vertical gaze deficits. The center for horizontal conjugate gaze is the paramedian pontine reticular formation (PPRF) in the pons, whereas the structure that generates vertical saccades is the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) in the midbrain. Therefore, this combination of ocular motor deficits cannot be explained by a single anatomic lesion. This patient must have either multiple brainstem lesions or a nonstructural disease process.

What metabolic abnormality can produce this clinical picture?

Wernicke’s encephalopathy is a neurologic syndrome caused by thiamine (B1) deficiency and

characterized clinically by ophthalmoplegia, ataxia and confusion. The full triad, however, is present in only a minority of cases. It is therefore important to be able to recognize this condition based on parts of the complete syndrome. Ocular motility disturbance is the earliest and most constant finding in this disorder. Based on the patient’s history of persistent vomiting, a presumptive diagnosis of Wernicke’s encephalopathy was made. A brain MRI was normal. The patient was treated with 100 mg of thiamine intravenously and showed marked improvement of signs and symptoms within two to three days. She was discharged on anti-emetics and oral thiamine supplementation, and the remainder of her pregnancy was uneventful.

Discussion: Wernicke’s encephalopathy is a preventable cause of neurologic morbidity in which prompt recognition and treatment directly influence the clinical outcome. The key to making this diagnosis is a high index of suspicion based on an awareness of the risk factors for thiamine depletion. These include persistent vomiting of any cause (e.g. hyperemesis gravidarum, gastrointestinal disorders or chemotherapy) and nutritional deficiency states such as chronic alcoholism, prolonged intravenous alimentation and malignancy (see Table 9.1). A new category of high-risk patients has emerged

148Chapter 9: Neuro-ophthalmic look-alikes

Table 9.1 High-risk groups for thiamine deficiency and Wernicke’s encephalopathy

Chronic alcoholism

Protracted vomiting (e.g. hyperemesis gravidarum) Gastric resection and intestinal bypass

Starvation state (e.g. anorexia nervosa, radical diets) Long-term intravenous alimentation

Chronic renal dialysis Leukemia

Children with malignancy

Certain dietary restrictions (e.g. flour not enriched with thiamine)

in recent years with the increasing popularity of gastric surgery for obesity. Patients may be embarrassed about having had bariatric surgery and thus may not volunteer this aspect of their history, particularly during an evaluation for acute diplopia.

Ocular motor dysfunction is typically the earliest sign of Wernicke’s encephalopathy. This may be as subtle as small-amplitude horizontal end-gaze nystagmus or slowing of saccades. Abduction weakness is common, sometimes manifest as just an esodeviation without a ductional deficit. Conjugate gaze palsies, which may be horizontal, vertical, or both, are present in almost half of cases. Upbeat nystagmus is also characteristic, due to disruption of the pathways connecting the anterior semicircular canal, cerebellum and brachia of the midbrain (see Table 9.2). About 30% of patients with Wernicke’s encephalopathy have isolated or predominant mental status changes ranging from apathy, confusion and somnolence to delirium and frank coma. When the onset of symptoms is abrupt, Wernicke’s encephalopathy may be mistaken for a stroke syndrome. This is particularly true in patients with sudden onset of a confusional state accompanied by esotropia. The presence of symmetric lesions in the paramedian thalamus in such cases may further add to the impression of a “top-of- the-basilar syndrome”, i.e. occlusion of the posterior thalamoperforating arteries. In this clinical setting, an empiric trial of thiamine may have both diagnos-

Table 9.2 Causes of upbeat nystagmus

Wernicke’s encephalopathy Multiple sclerosis Cerebellar degenerations

Focal lesions of vestibulocerebellum (tumor, stroke) Midbrain lesions (tumor, stroke)

Brainstem encephalitis Meningitis

Thalamic vascular malformation Congenital

Organophosphate poisoning

Transient phenomenon in normal infants

tic and therapeutic value. Patients with Wernicke’s encephalopathy typically experience rapid clearing of mental status and resolution of esotropia, whereas patients with stroke show no beneficial response.

The diagnosis of Wernicke’s encephalopathy is made on clinical grounds. MRI findings, when present, can provide additional supportive evidence. Lesions are often symmetric with a predilection for the mamillary bodies, periventricular region of the third ventricle, medial thalamus, periaqueductal gray and midbrain tegmentum, seen best as hyperintensities on T2 and FLAIR sequences or as enhancement on post-contrast T1-weighted images (Figure 9.11). These abnormalities are quite specific for Wernicke’s (93% specificity), but have relatively low sensitivity, present in only half of patients who are imaged within two weeks of symptom onset. Low serum erythrocyte transketolase activity confirms a state of thiamine deficiency but this test result may take days to obtain. Because the neurologic deficits of Wernicke’s are reversible with prompt thiamine repletion, it is important to treat on suspicion, based on the clinical features as described above, rather than waiting for laboratory confirmation. Treatment usually starts with 100 mg of thiamine given intravenously or intramuscularly with glucose supplementation. Clinical manifestations often resolve within hours of thiamine repletion. Untreated, the condition can be life-threatening and associated with significant