neurologic morbidity, including Korsakoff’s amnesia as well as oculomotor and other brainstem deficits.

The clinical scenario: Conjugate gaze palsy and upbeat nystagmus

The look-alikes: Brainstem stroke vs. thiamine depletion (Wernicke’s encephalopathy)

Tip: Eye movement abnormalities in Wernicke’s encephalopathy are varied, and the classic clinical triad is frequently incomplete. Recognizing that the patient is at risk for thiamine deficiency is key to making the diagnosis.

Chronic progressive external ophthalmoplegia vs. progressive supranuclear palsy

Case: A 64-year-old retired plumber noted difficulty reading and trouble refocusing between distance and near. He was generally healthy but described progressive difficulty with balance for the preceding two years. Afferent visual function, pupillary examination and biomicroscopy were normal. Ocular motility testing revealed moderate limitation of horizontal eye movements and profound impairment of vertical gaze, especially downgaze, which was essentially absent. Saccades in all directions were markedly slowed. He had a small esophoria at distance and larger exophoria at near.

This combination of horizontal and vertical gaze limitation with slowed saccades could be due to either supranuclear gaze palsy or ocular myopathy. How can we distinguish these two mechanisms?

The status of reflex eye movements should differentiate these two disorders. The vestibulo-ocular reflex (Doll’s head maneuver) is preserved, and even enhanced, in supranuclear gaze palsy, whereas in ocular myopathy (or any other disorder from the nucleus to the eye muscles), ocular excursions are no greater with reflex movements.

Although this patient had virtually no voluntary eye movement below midposition, when asked to fixate a target while his head was quickly tipped back, downgaze was full (Figure 9.12). The range of eye movements in other directions was similarly improved with reflex maneuvers. In performing this test, it was noted that there was some resistance to passive head movements. He also displayed a decreased blink rate and a general paucity of facial expression. Based on these clinical features,

a diagnosis of progressive supranuclear palsy (PSP) was made.

Discussion: Progressive supranuclear palsy is an idiopathic neurodegenerative disease characterized by parkinsonian features, subcortical dementia and supranuclear gaze palsy. The earliest manifestation is usually a non-specific gait disorder which usually precedes other symptoms by about two years. At this stage, it is not usually possible to make a definitive diagnosis. As the disease progresses, accurate diagnosis remains a challenge, reflected in the mean time from symptom onset to diagnosis of about four years. Typical neurologic features include increased axial tone, bradykinesia, dysarthria and dysphagia. Three clinical types of PSP have recently been distinguished. The most common is the classic syndrome described by Steele et al., in which falls occur early in the course, tremor is absent, neurologic signs are symmetric and response to levodopa is poor. In one-third of patients, falls are delayed in onset and there is tremor, asymmetry, and a

positive, though unfortunately transient, response to levodopa. Less commonly, gait apraxia is the initial and most prominent manifestation. With rare exceptions, ocular motor deficits are prominent in all three subtypes.

Most patients exhibit progressive loss of voluntary conjugate gaze, initially affecting vertical movements more than horizontal, and involving both pursuit and saccades. Prominent slowing of saccadic velocity is an invariable and sensitive sign. Pursuit is saccadic, consistent with cerebellar involvement, but nystagmus is not prominent due to loss of the fast (refixation) component. As the name indicates, the ophthalmoplegia in this disease is supranuclear so that reflex eye movements (Doll’s head, Bell’s phenomenon) are preserved as voluntary gaze is progressively lost. In more advanced cases, the Doll’s head maneuver may be difficult to perform due to increased axial tone causing resistance to passive neck movement.

Vergence movements are also impaired, causing an exodeviation at distance and esodeviation at near. When diplopia occurs, it is due to this misalignment at varying distances rather than an imbalance in conjugate eye movements. Fixation is unstable, interrupted by frequent saccadic intrusions, termed macro square wave jerks based on their appearance on infrared oculography. The blink rate is decreased and some patients also experience blepharospasm and/or apraxia of eyelid opening. The constellation of eye movement abnormalities in this disease is so characteristic that the diagnosis can usually be made on clinical grounds.

There is no definitive test to confirm a diagnosis of PSP but clinical criteria established for research purposes have proved highly sensitive and specific. In addition, several characteristic MRI changes have been described. Atrophy of the dorsal midbrain is most prominent, sometimes causing an appearance on mid-sagittal sections termed the “hummingbird sign” in which thinning of the midbrain tegmentum mimics the tapered head and long, narrow beak of this bird (Figure 9.13). Additional changes that similarly reflect the predilection for certain areas of the brain in this disease include dilation of the posterior

Figure 9.13 Mid-sagittal non-contrast T1-weighted MRI of a patient with PSP, showing the “hummingbird sign” due to thinning of the rostral end of the midbrain tegmentum (arrow). The tectal plate is thin and flat. (Photo courtesy of Dr. Benjamin Kuzma.)

third ventricle, atrophy of the anterior temporal lobes, iron deposition in the lateral putamen and wisps of high-T2 signal in the midbrain and pons due to gliosis. The role of functional imaging in the diagnosis of this disorder remains to be established.

Central cholinergic deficits are thought to be the basis for the postural instability, gait disturbance and cognitive impairment associated with PSP, however cholinergic replacement therapies have been generally ineffective. Management in patients with PSP remains symptomatic (see Chapter 12, Failure to provide symptomatic treatment). Unfortunately, the disease is relentlessly progressive and is usually fatal on average seven years after onset of symptoms.

Chronic progressive external ophthalmoplegia (CPEO) is similarly characterized by progressive, symmetric, bilateral loss of voluntary eye movements affecting horizontal and vertical gaze. The biochemical defect in this disorder consists of mutations or deletions of mitochondrial DNA that encode respiratory chain enzymes involved in the