S E C T I O N
12 Neurologic Disorders
106 ACQUIRED INFLAMMATORY DEMYELINATING NEUROPATHIES
355.9
(Guillain–Barré Syndrome or Acute Inflammatory Demyelinating Polyradiculoneuropathy [AIDP], Chronic Inflammatory Demyelinating Polyradiculoneuropathy [CIDP], and Fisher Syndrome)
Paul W. Brazis, MD
Jacksonville, Florida
Andrew G. Lee, MD
Iowa City, Iowa
ETIOLOGY/INCIDENCE
Guillain–Barré syndrome (GBS) (acute inflammatory demyelinating polyradiculoneuropathy, or AIDP) can occur at any age and has an estimated annual incidence of approximately 1 to 2 cases in 100,000.
In at least two thirds of patients with GBS, a history of premonitory illness, usually viral, can be elicited by taking a careful history. Cytomegalovirus, Epstein–Barr virus, and human immunodeficiency virus (HIV) have been most closely associated with the condition. Infection by organisms of the Campylobacter genus has drawn much attention, with some reports suggesting that enteritis caused by species of Campylobacter occurs in as many as 15% to 20% of GBS patients. In addition to antecedent infections, Hodgkin’s disease and recent surgery are well-recognized premonitory events.
evolving cases, respiratory paralysis can occur within the first few days. About one third of hospitalized GBS patients eventually develop respiratory insufficiency. The diagnostic criteria for typical GBS require:
●Weakness that is symmetric in all limbs;
●Paresthesias in the hands and feet;
●Hyporeflexia or areflexia in all limbs by the end of the first week; and
●Progression of the weakness, paresthesias, and reflex abnormalities over several days to one month.
Guillain–Barré syndrome
●The overall prognosis for the majority of GBS patients is good, but 5% to 10% develop significant clinical impairment that precludes routine activities of daily living.
●Vedeler and colleagues reported the long-term outcome of 52 patients reexamined over a mean of 7 years. Of the 52 patients, 38 (73%) were free of symptoms. Neurologic examination revealed motor abnormalities in 21%, sensory signs in 31%, cranial neuropathy in 2%, and areflexia in 29%. Treatment with plasma exchange did not influence disability grade.
●In a retrospective questionnaire study of 175 patients with GBS, at the peak of disease 26% remained able to walk and 16% had to be artificially ventilated. The median time from onset of symptoms to ability to walk unaided was 37 days, and from onset to freedom from symptoms, 66 days. At long-term follow-up, 98 of 106 patients were symptom free.
●Mortality rate remains 2% to 5%, with most patients dying from pulmonary infections, sepsis, pulmonary emboli, or complications of autonomic instability.
●Risk factors for poor outcome include older age, ventilator dependence on admission, a rapid rate of disease progression (e.g. reaching nadir of weakness in less than 1 week), and low-amplitude motor responses on nerve conduction studies.
COURSE/PROGNOSIS
The initial symptoms are almost invariably sensory-numbness and tingling in the fingers and toes and, occasionally, even on the trunk. Subsequently, weakness develops in the legs, with later involvement of the upper extremities. Weakness is the predominant clinical feature of GBS; it is the manifestation that results in hospitalization for most patients, and it is usually both proximal and distal and involves the facial muscles in 30% to 40% of patients. Muscle stretch reflexes are absent or depressed. Although approximately 90% of cases reach their nadir by 4 weeks, the tempo of progression is variable. In rapidly
Chronic inflammatory demyelinating polyradiculoneuropathy
●CIDP is a chronic and serious disorder.
●Approximately 95% of patients with CIDP initially improve with prednisone treatment, but the relapse rate is very high. In one series, 50% of patients relapsed after a mean followup period of 49 months; only 51% made a complete recovery. Two patients who initially responded later died from complications of the disease.
●In the studies of Dyck and colleagues, 64% of 53 patients were improved or in remission and able to return to work, 8% were ambulatory but unable to work, 11% were bedrid-
201
Disorders Neurologic • 12 SECTION
den or wheelchair-bound, and 11% died of the disease; 6% died of other diseases.
DIAGNOSIS
Fisher syndrome is a variant of GBS and represents about 5% of GBS cases. The major criteria for the diagnosis are external ophthalmoplegia, ataxia and areflexia without significant muscle weakness. The disease is usually self-limited and relatively benign. Its course and the frequent (10% to 20%) occurrence of ophthalmoplegia in typical cases of GBS are the main reasons for its acceptance as a subtype of GBS. Anti-GQ1b antibodies may be identified in the serum in approximately 95% of patients with Fisher syndrome. Eye movement abnormalities that occur with GBS include palsies of cranial nerves III, IV, VI, or all three, complete ophthalmoplegia, pseudointernuclear ophthalmoplegia, rebound nystagmus and preserved Bell’s phenomenon with absence of upgaze. Other ocular complications of GBS include ptosis, lid lag, pupillary abnormalities (e.g. asymmetrically dilated and nonreactive pupils, light-near dissociation), impaired accommodation, impaired lacrimal secretions, reduced corneal sensation, trigeminal impairment, facial nerve palsies, unilateral or bilateral optic neuritis and papilledema.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a polyneuropathy whose course differs from GBS in that its progression is measured in months or years and it is generally not self-limited. CIDP can occur at any age but the ages of peak onset are between 40 and 60 years. Patients typically present with progressive, stepwise or relapsing muscle weakness. To fulfill the diagnostic criteria for CIDP, weakness must have been present for at least 2 months. Weakness varies from mild to severe, and some patients require assisted ambulation or wheelchairs. Sensory complaints are variable, usually consisting of numbness and tingling. Cranial nerve involvement includes facial weakness in 15% of cases; occasionally, patients have swollen optic disks or extraocular muscle impairment.
cases is still uncertain. Enough data have not been generated on ambulatory patients to be certain that the expense and discomfort can be justified.
●Considering the fact that plasma exchange and intravenous immune globulins are of equal benefit, final decisions regarding treatment of GBS relate more to individual patient considerations. For example, in an ICU setting in patients with poor venous access, cardiovascular instability, or concurrent infections, infusions of immune globulins may be indicated.
Ocular
●In patients with facial or trigeminal involvement, the cornea is threatened by the development of exposure and neuroparalytic keratitis. Thus, artificial tears, moisture chambers and lateral tarsorrhaphies may be warranted.
●Diplopia is treated with patching or prisms.
●Decreased accommodation may require reading glasses.
●Papilledema resolves spontaneously.
Supportive
●Careful monitoring of pulmonary function is critical; patients with a forced vital capacity below 12 to 15 mL/kg usually require endotracheal intubation.
●Chest physical therapy and prompt treatment of chest infections are important.
●Swings in blood pressure are common. In general, hypertension is manageable without medication, but hypotension may require pressor agents and fluid. Vagally mediated arrhythmias may require cardiac treatment.
●Heparin, 5000 units SC b.i.d., is indicated for the prevention of pulmonary emboli.
●GBS patients in an ICU setting are, of course, at high risk of acquiring nosocomial infections that must be treated promptly.
●Pain can be a significant practical problem, and narcotic analgesics are often required.
●Physical therapy is essential to ensure proper positioning; passive and active exercises maintain joint flexibility and minimize the likelihood of contractures.
TREATMENT
Guillain–Barré syndrome
Systemic
●Steroids are probably of no benefit, although a small uncontrolled series suggested that a combination of intravenous immune globulins (IVIG) and high-dose methylprednisolone may be better than IVIG alone.
●Two specific forms of therapy that have been shown to alter the natural history of GBS are plasma exchange and intravenous immune globulin.
●Plasma exchange: prospective, controlled studies involving more than 500 patients have shown definite evidence that plasma exchange benefits patients with GBS. Plasmapheresis significantly improves muscle strength by 4 weeks and decreases the number of days required to achieve assisted ambulation. In addition, patients with respiratory failure have significantly fewer days of ventilator dependence following plasma exchange. A standard regimen for plasma exchange in GBS patients involves removing 200 to 250 mL of plasma per kilogram of body weight over a 7- to 14-day period. Therapy should be instituted as soon as possible following diagnosis. The role of plasma exchange in mild
CIDP
Systemic
●Randomized controlled studies have documented the effectiveness of prednisone plasma exchange, and IVIG. These forms of therapy represent the mainstay of treatment for CIDP.
●Following diagnosis of CIDP, high-dose daily prednisone is maintained until the patient shows significant improvement. The mean time for initial response to treatment is 2 months; by 3 months, 88% improve. Following improvement, the dose is changed to an alternate-day, single-dose regimen that is maintained until the patient reaches a maximum therapeutic response-that is, return to normal or reach a plateau.
●After the patient has attained maximum benefit from it, prednisone is slowly tapered. Plasma exchange added to the initial prednisone treatment regimen significantly diminishes the time necessary for improvement.
●Intravenous immune globulin appears to produce clinical improvement in some patients with CIDP.
●Other immunosuppressing drugs are often considered for refractory disease. They include azathioprine, cyclophosphamide, methotrexate, ciclosporin, mycophenolate mofetil,
202
pulse methylprednisolone, interferon-alpha 2a, and total lymphoid radiation but the potential toxicity of these agents must be carefully considered.
Supportive
●Patients with CIDP are rarely ventilator-dependent, seldom have bulbar impairment, and are usually ambulatory, although they may need assistance.
●The major problem is rehabilitation. Physical therapy is important, especially during steroid treatment, to preserve and improve muscle strength. Bracing and other aids may be necessary.
●As CIDP is a chronic and often debilitating disease, psychologic support is essential.
REFERENCES
Dalakas MC: Intravenous immune globulin therapy for neurologic diseases. Ann Int Med 126:721–730, 1997.
Donofrio PD: Immunotherapy of idiopathic inflammatory neuropathies. Muscle Nerve 28:273–292, 2003.
The Dutch Guillain-Barré Study Group: Treatment of Guillain-Barré syndrome with high-dose immune globulins combined with methylprednisolone: a pilot study. Ann Neurol 35:749–752, 1994.
Dyck PJ, Daube J, O’Brien P, et al: Plasma exchange in chronic inflammatory demyelinating polyradiculopathy. N Engl J Med 314:461–465, 1986.
Dyck PJ, Lais AC, Ohta M, et al: Chronic inflammatory demyelinating polyradiculoneuropathy. Mayo Clin Proc 50:621–637, 1975.
Dyck PJ, O’Brien PC, Oviatt KF, et al: Prednisone improves chronic inflammatory demyelinating polyradiculoneuropathy more than no treatment. Ann Neurol 11:136–141, 1982.
Gorson KC, Ropper AH, Clark BD, et al: Treatment of chronic inflammatory demyelinating polyneuropathy with interferon alpha-2a. Neurology 50:84–87, 1998.
Korinthenberg R, Monting JS: Natural history and treatment effects in Guillain-Barré syndrome: Multicentre study. Arch Dis Child 74:281– 287, 1996.
McKhann GM, Griffin JW, Cornblath DR, et al: Plasmapheresis and Guil- lain-Barré syndrome: analysis of prognostic factors and the effect of plasmapheresis. Ann Neurol 23:347–353, 1988.
Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group: Randomized trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome. Lancet 349:225– 230, 1997.
Ropper RH: The Guillain-Barré syndrome. N Engl J Med 326:1130–1136, 1992.
Van Doorn PA, Brand A, Strengers PFW, et al: High-dose intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy: a double-blind, placebo-controlled, crossover study. Neurology 40:209–212, 1990.
Van der Meché FG, Schmitz PIM, the Dutch Guillain-Barré Study Group: a randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barré syndrome. N Engl J Med 326:1123– 1129, 1992.
Vedeler CA, Wik E, Nyland H, et al: The long-term prognosis of GuillainBarré syndrome: Evaluation of prognostic factors including plasma exchange. Acta Neurol Scand 95:298–302, 1997.
107 BELL’S PALSY 351.0
(Idiopathic Facial Paralysis)
Michael S. Harney, MD, MB, FRCSI (ORL)
Dublin, Ireland
Rory McConn Walsh, MD, MB FRCSI (ORL)
Dublin, Ireland
ETIOLOGY/INCIDENCE
The facial nerve is the most commonly paralyzed nerve in the body (Figure 107.1). The most common cause is Bell’s palsy occurring at a rate of 20/100,000 per year. Though sometimes termed ‘idiopathic facial nerve palsy’, this is probably a herpetic induced neuritis, resulting in inflammation, subsequent entrapment in the tight confines of the temporal bone, causing ischemia and finally degeneration. Optimum management of this condition requires attention to three key principles:
●A correct diagnosis; It is important to ensure a more serious diagnosis of cerebrovascular accident, acoustic neuroma, middle ear disease or a parotid tumor is not missed.
●Minimizing the number of patients left with a residual nerve deficit.
●Anticipation and management of secondary ocular complications.
COURSE/PROGNOSIS
This condition classically occurs in otherwise healthy individuals. Patients will present to the health professional with a facial nerve weakness that has developed over a period of several hours to days. The history will often yield a recent viral illness. Occasionally, otalgia and a perception of some sensory change on the affected side will be present. The patient may complain of decreased tearing, epiphoria, dysgeusia or hyperacusis.
Most patients will show signs of recovery of facial function within 3 weeks, though in some remission may occur up to 6 months later. Eighty-three percent of patients will have full recovery, but 17% will be left with some residual neurological sequelae. A complete palsy carries a worse prognosis. Permanent sequelae result from abnormal weakness of the facial musculature (cosmetic deformity, lagopthalmus, ectropion) or from abnormal reinnervation of damaged nerve fibers (synkinesis, crocodile tears [tearing on eating], hemifacial spasm).
DIAGNOSIS
The first step in making a correct diagnosis of Bell’s palsy is ensuring the palsy is a lower motor lesion. This is done by asking them to raise their eyebrows, to tightly close their eyes and to show their teeth. Patients with a lower motor lesion will demonstrate weakness in performing all three maneuvers. Those with an upper motor lesion will only display impairment of function with the last of these commands, due to contralateral innervation of the upper facial musculature. The most common cause of an upper motor facial nerve weakness is a cerebrovascular accident.
Having determined the palsy is lower motor, the second step is to ensure that there is not another cause for the palsy. Bell’s
107 CHAPTER Palsy Bell’s •
203
Disorders Neurologic • 12 SECTION
FIGURE 107.1. Seventh nerve palsy.
palsy remains a diagnosis of exclusion. Examination should include:
●Otoscopy to out rule many of the reversible causes of facial nerve palsy; acute otitis media, chronic suppurative otitis media, cholesteatoma and Ramsay–Hunt syndrome. Ear discharge (otorrhoea) should prompt urgent referral to an otolaryngologist as this strongly suggests an otological cause requiring surgery. Ramsay–Hunt syndrome (herpes zoster oticus) is diagnosed by the presence of vesicular eruptions on the pinna or in the ear canal.
●Parotid gland examination. The presence of a facial nerve palsy in the presence of a parotid mass indicates the mass is malignant.
eye may remain open underneath. Occasionally, a lid mattress suture in the skin of the upper lid, taping the ends firmly to the upper cheek, can be performed to close the eyelid.
●Punctal plugs might be helpful if dryness of the cornea is a persistent problem.
●Rarely, clear plastic wrap, cut to 8 × 10 cm and applied with generous amounts of ointment, can be used as an occlusive bandage at night.
Failure of Bell’s palsy to resolve may require local treatment of its sequelae:
●Lower lid ectropion, or droop, can be temporarily helped by using tape applied below the lid margin in the center of the lower lid, pulling the lid laterally and upward to anchor it on the orbital rim;
●Botulinum toxin injected in to the levator palpebrae superioris muscle through the eyelid can produce a protective ptosis possibly avoiding the need for a lateral tarrsorraphy.
Surgical
The theory of nerve dysfunction as a result of entrapment in the fallopian canal in the temporal bone, secondary to edema, gave rise to the practice of surgically decompressing the facial nerve. Serious complications such as permanent hearing loss may occur and the role for surgery in a virally induced neuritis is contentious. Restoration of facial nerve function may be
●Examination of the cranial nerves particularly the trigemiconsidered using a hypoglossal to facial nerve anastomosis.
nal nerve and the vestibulocochlear nerve with tuning fork tests and audiometry if possible. These may be involved by an acoustic neuroma (or other cerebellopontine angle [CPA] lesions)
●The skin for the presence of erythema migrans in areas where Lyme disease is endemic.
If the above examinations are normal and the palsy is confirmed to be lower motor then the diagnosis is Bell’s palsy. No further investigations are necessary at this stage except for lyme titres in endemic areas. An MRI should be done if the palsy fails to resolve at 6 weeks or if atypical symptoms are present to out rule a more sinister underlying cause.
TREATMENT
Systemic
Most clinicians would treat bells palsy with both steroids and aciclovir though neither have been shown to be clearly effective. Oral steroids may reduce inflammation in the facial nerve with a reduction in subsequent ischemia and degeneration. Antiviral agents may be useful if the disease is caused by a herpetic virus.
Local
The immediate aim of local treatment should be to prevent corneal exposure and subsequent ulceration.
●In most cases, topical ocular lubrication is sufficient (artificial tears frequently during the day and lubricating ophthalmic ointment at night; occasionally, ointment must be used around the clock).
●The eye may be taped at night using tape or adhesive strips (Steristrips). Caution must be exercised with patches as the
Regional muscle transfers may also be attempted using temporalis muscle. A period of twelve months to allow for spontaneous recovery should be observed prior to undertaking these procedures.
Surgical treatment of the eye is required in the unusual instance of a Bell’s palsy that fails to recover. It is more often required in facial nerve injury following acoustic neuroma surgery (or other CPA surgery), parotid tumour removal, or following trauma with a temporal bone fracture. Surgery for CPA lesions is of particular importance as there is often associated trigeminal paresis with corneal anesthesia.
●Lagopthalmus can be treated with lateral tarsorrhaphy. This decreases horizontal lid opening, provides better support of the precorneal lake of tears, and provides better coverage of the eye during sleep. This can be reversed if recovery occurs. To restore dynamic lid closure in cases of severe, symptomatic lagophthalmos, a variety of ingenuous devices have been invented. All overcome the elevator action of the levator palpebrae muscle. Weightadjustable magnets, gold weights, palpebral springs, or silicone encircling bands can be inserted into the eyelids. These devices require close observation because they can extrude.
●Lower lid ectropion can be managed by a horizontal lid wedge shortening.
●Punctal ectropion causing epiphoria may be repaired with removal of a horizontal tarsoconjunctival ellipse of tissue inferior to the lower lid punctum (protecting the canaliculus with a probe), suturing the edges of the ellipse together.
●Medial ectropion with punctual eversion may benefit from a medial canthoplasty combined with horizontal shortening of the lower lid and a tarsoconjunctival ellipse.
204
COMMENTS
Bell’s palsy is a diagnosis of exclusion. It is important to examine the ear to exclude many of the reversible causes of facial nerve palsy. No treatments have shown to be clearly effective though most clinicians will treat with both oral steroids and aciclovir. A clinician can be reassured that if the palsy is incomplete, 94% recover completely within months. Electrophysiological testing does not have a role to play in routine cases. Exercises may be useful and can give the patient the feeling that they are taking an active role in their own recovery. An MRI scan should be performed if the patient fails to recover, or demonstrates atypical signs, to exclude the remote possibility of a more sinister underlying cause. Topical ocular therapy is sufficient in the majority of cases of Bell’s palsy.
REFERENCES
Ellis MF, Daniell M: An evaluation of the safety and efficacy of botulinum toxin type A (BOTOX) when used to produce a protective ptosis. Clin Experiment Ophthalmol 29(6):394–399, 2001.
Fisch U: Surgery for Bell’s palsy. Arch Otolaryngol 107(1):1–11, 1981.
Peiterson E: Bell’s palsy: the spontaneous course of 2500 peripheral facial nerve palsies of different etiologies. Acta Otolaryngol Suppl 549:4–30, 2002.
Salinas RA, Alvarez G, Alvarez MI, Ferreira J: Corticosteroids for Bell’s palsy (idiopathic facial paralysis). Cochrane Database Syst Rev 1: CD001942, 2002.
Schirm J, Mulkens PS: Bell’s palsy and herpes simplex virus. APMIS 105:815–823, 1997.
Sipe J, Dunn L: Aciclovir for Bell’s palsy (idiopathic facial paralysis). Cochrane Database Syst Rev 4:CD001869, 2001. Update in: Cochrane Database Syst. Rev. 3:CD001869, 2004.
108 CEREBRAL PALSY 343.9
(Brain Damage Syndrome, Perinatal
Encephalopathy)
F. Hampton Roy, MD, FACS
Little Rock, Arkansas
ETIOLOGY/INCIDENCE
Cerebral palsy is a group of conditions with widely diverse etiologies; these conditions arise as a result of brain damage that occurs before, during, or shortly after birth. In utero exposure to rubella or cytomegalovirus or placental insufficiency may result in brain damage and cerebral palsy; prematurity, precipitate labor, neonatal asphyxia and hypoxia, hypoglycemia, hyperbilirubinemia, and accidents during labor and delivery also are known to cause the condition. Neonatal meningitis, encephalitis, and trauma also have been implicated as causative. In addition, in about 10% of children with cerebral palsy there is no known cause, despite extensive investigation. It appears to be familial in a very small number of cases.
DIAGNOSIS
Clinical signs and symptoms
The disorders cerebral palsy comprises are not progressive but are not unchanging. They are dominated by motor abnormalities. Associated with the motor dysfunction are varying degrees of:
●Mental subnormalities;
●Emotional instability;
●Convulsive disorders;
●Abnormalities of hearing;
●Speech defects;
●Visual abnormalities.
Cerebral palsy is usually classified according to the motor abnormality and its topography; spastic, ataxic and athetoid forms are most common, appearing in isolation or, less commonly, in combination. Except in athetoid cerebral palsy, it is rarely possible to localize the site of the causative lesion in the brain; the broad array of associated disabilities reflects the diffuse and widespread nature of the nervous system lesions.
Ocular
Abnormalities of the visual apparatus are common in cerebral palsy; the incidence of ocular changes has been reported to be between 50% and 80% of cases. The range of disorders is wide and can include:
●Esophorias and exophorias;
●Hypertropia, esotropias, and exotropias;
●Paralysis of third, fourth and sixth cranial nerves;
●Gaze palsies;
●Epicanthus, ptosis;
●Refractive errors;
●Amblyopia;
●Leukomas;
●Nystagmus;
●Cataracts;
●Iris coloboma, heterochromias;
●Visual field defects;
●Microphthalmos;
●Chorioretinal scars, coloboma, pigmentary degeneration;
●Retinopathy of prematurity;
●Optic nerve hypoplasia, coloboma, atrophy;
●Cortical visual impairment.
Spastic types of cerebral palsy are most likely to have associated ocular abnormalities, whereas purely athetoid types are the least likely. There is some evidence that the incidence of ocular abnormality rises with the degree of mental subnormality; however, an ocular abnormality rate of 70% has been reported in children with cerebral palsy who have normal or near-normal intelligence. Problems caused by the ocular abnormalities are compounded by visuospatial and perceptual difficulties that result from the underlying brain damage.
TREATMENT
Ocular
Refractive errors are common.
●Myopia: associated with prematurity.
●Hyperopia: most often found in those children whose cerebral palsy is not due to prematurity.
108 CHAPTERPalsy Cerebral •
205
Disorders Neurologic • 12 SECTION
If possible, children with normal or near-normal intelligence should have full correction of any refractive errors detected by a subjective refraction; this is frequently impossible, however, and in these cases an objective refraction should be carried out after instillation of a cycloplegic agent such as atropine (1.0%) or cyclopentolate (1.0%), depending on the child’s age.
The level at which refractive errors should be corrected in those who are severely subnormal has been a matter of some discussion in the literature. Small refractive errors should be corrected only in those who are likely to benefit from such corrections; larger refractive errors should be corrected in all children with cerebral palsy, in whom the acceptance of spectacle correction is usually very good.
Those children at risk of amblyopia due to anisometropia or squint should be identified at an early age so that appropriate therapy for amblyopia can be carried out. Some infants appear to have an isolated deficit of accommodation that may require correction. At the same time, a thorough examination of the fundus and the optic nerve can be performed, particularly with the indirect ophthalmoscope.
Strabismus is detected in the usual manner in patients with cerebral palsy; there is a far higher incidence of divergent and incomitant strabismus in children with cerebral palsy than in children who are neurologically normal. Moreover, a variable strabismus angle is common and, in some cases, the deviation may be divergent or convergent at varying times. In addition, approximately 25% of children with concomitant squint have a retinal or optic nerve abnormality that precludes an improvement in visual acuity.
Full correction of any refractive error based on a cycloplegic refraction must be made, followed by:
●Occlusion of the squinting eye;
●Orthoptic treatment, if appropriate.
Rarely, treatment may involve the use of:
●Prisms;
●Anticholinesterase eyedrops (occasionally).
It is important, however, to guard against adverse reactions that may occur with the use of anticholinesterase compounds in this group of children. The aim of treatment is to give the child binocularity or at least good vision in both eyes before surgery, if surgery is indicated. There is some evidence that successful treatment of strabismus may improve a child’s coordination.
Surgical
For nonaccommodative esotropia and exotropia, recession and resection of the appropriate muscles are usually adequate treatments. The degree to which the horizontal muscles are weakened or strengthened must be determined by repeated observation because of the variable angles often found in strabismus in these children. Particularly when squint presents a purely cosmetic problem and one eye has very poor vision that cannot be improved, the aim should be to undercorrect the deviation, to counteract the tendency to overcorrect.
Vertical deviations are fairly common; most of them manifest as overaction of the inferior oblique muscles, for which there may be several causes. In these cases, simple recession or myotomy of the inferior oblique muscle is satisfactory treatment.
In very young children, bilateral cataract/lens aspiration or lensectomy/vitrectomy may be carried out; subsequent optical correction with contact lenses or spectacles may pose special
problems and difficulties, however. In older children in whom cataracts develop, appropriate cataract surgery can be carried out with the insertion of a posterior chamber lens implant. Although the use of intraocular lenses in children remains controversial, there may be a special place for their use in young patients who have severe behavioral or emotional problems or motor disabilities.
Rarely, other abnormalities amenable to surgical correction such as congenital glaucoma may be seen and should be treated along conventional lines.
Supportive
The aim of examination is to identify at an early age those defects that are treatable and to undertake treatment for them as if the child were otherwise normal. Many studies have shown that ocular disabilities in children with cerebral palsy are detected much later than in children who are normal.
It is equally important to identify children with severe visual impairment that is not amenable to treatment; the ophthalmologist is then in a position to counsel parents on the placement of their children in the correct educational environment. Those who will be responsible for assessing the children’s intellectual abilities and those who will educate them have to be aware of each one’s visual status. Teachers, in particular, have to understand the visual acuity, the size of the visual field, and the ability to match colors of the children in their care. Many of these children are deaf and their education relies heavily on visual stimulation.
The ophthalmologic findings in cerebral palsy cannot be taken in isolation; assessment and treatment must be coordinated with many other disciplines. To this end, the ophthalmologist should be part of a multidisciplinary team that includes psychologists, teachers and other physicians concerned with the welfare of the children. There is continual need for reassessment as the children grow and parents and teachers need constant reassurance. The aim of the ophthalmologist must be to provide the children with the best possible chance of attaining independence, or at least to minimize the amount of institutional care required when they leave the shelter of school.
PRECAUTIONS
Examination of children with cerebral palsy is often difficult, particularly when there is mental subnormality. Subjective tests, such as those for visual acuity, are unreliable and the examination may have to be repeated on several occasions before the ophthalmologist can be sure of the findings.
Newer methods of assessing visual acuity, such as the use of visual evoked potentials and the techniques of forced preferential looking, may be particularly useful in those patients who are mentally subnormal. It is easy to underestimate a child’s visual capabilities, especially in those with gross disturbances of motility such as athetosis and in those with hemianoptic field defects.
Young, severely handicapped children should be examined in familiar surroundings, preferably with someone they know and trust alongside them. Doing so allays their fears and is imperative in cases in which deafness or speech impairment requires their responses to be interpreted.
Topical drugs with known systemic side effects should be used with caution; there are reports (largely anecdotal) that these children are unusually prone to developing adverse reac-
206
tions to some types of eyedrops. It is important that surgical therapy, usually for strabismus, be planned in consultation with the other disciplines concerned with the medical care of such children, as these patients often are subjected to multiple surgical procedures, particularly for musculoskeletal problems. Few guidelines exist on the management of strabismus in these children, but the information that is available suggests that squints should be treated as they would be if the child were otherwise normal.
COMMENTS
It is apparent from the literature that visual problems in children with cerebral palsy are commonly overlooked or ignored because they are overshadowed by the more dramatic musculoskeletal and intellectual deficits. Diagnosis of cerebral palsy usually has been made by the time children are 12 months old, however, and the initial ophthalmologic examination also should have been made by this time. Prompt initiation of treatment for probable amblyopia, or at least a plan for such therapy, should be made; continued reassessment is necessary, particularly before these children start school; so that appropriate decisions regarding training can be made at the earliest opportunity.
The ultimate aim for medical care and training is to enable children with cerebral palsy to become independent; this aim is not feasible in severely affected patients, but such severity may not be apparent until the second decade of life. All possible help is required by the children before then. To this end, every treatable defect should be identified at a sufficiently early age to allow appropriate measures to be carried out.
REFERENCES
Black PD: Visual disorders associated with cerebral palsy. Br J Ophthalmol 66:46–52, 1982.
Case-Smith J: Fine motor outcomes in preschool children who receive occupational therapy services. Am J Occup Ther 50:52–61, 1996.
Coltarello J, LeGare M, Terdiman J: Eye movements in a small sample of cerebral palsied adults. Percep Mot Skills 80:355–369, 1995.
Crofts BJ, King R, Johnson A: The contribution of low birth weight to severe vision loss in a geographically defined population. Br J Ophthalmol 82:9–13, 1998.
Dowdeswell HJ, Slater AM, Broomhall J, Tripp J: Visual deficits in children born at less than 32 weeks’ gestation with and without major ocular pathology and cerebral damage. Br J Ophthalmol 79:447–452, 1995.
Gormezano SR, Kaminski JE: The eye care profile and outcomes of multihandicapped adults residing in Wayne County, Michigan group homes. Optometry 76(1):19–29, 2005.
Jacobson L, Ygge J, Flodmark O, Ek U: Visual and perceptual characteristics, ocular motility and strabismus in children with periventricular leukomalacia. Strabismus 10(2):179–183, 2002.
Lee SK, LeGare M, Zhang HP: Conjugate eye movements: comparison of cerebral palsied and normal adults. Percep Mot Skills 81:575–591, 1995.
O’Keefe M, Kafil-Hussain N, Flitcroft I, Lanigan B: Ocular significance of intraventricular haemorrhage in premature infants. Br J Ophthalmol 85(3):357–359, 2001.
Orel-Bixler D, Haagerstrom-Portnoy G, Hall A: A visual assessment of the multiply handicapped patient. Optom Vis Sci 66:530–536, 1989.
Schiemann MM: Optometric findings in children with cerebral palsy. Am J Optom Physiol Optics 61:321–323, 1984.
109 CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA (CPEO) 359.1
(Abiotrophic Ophthalmoplegia, CPEO with Ragged Red Fibres, Oculocraniosomatic Neuromuscular Disease, Ocular Myopathy, Olson’s Disease, Kearns–Sayre–Daroff Syndrome, Kearns–Sayre Syndrome, Progressive External Ophthalmoplegia Plus)
Judith A.M. van Everdingen, MD
Rotterdam, The Netherlands
Jan-Tjeerd de Faber, MD
Rotterdam, The Netherlands
ETIOLOGY/INCIDENCE
Chronic progressive external ophthalmoplegia (CPEO) includes a spectrum of clinical findings that usually becomes apparent between the second and fourth decades as a syndrome of bilateral, painless, and pupil sparing, slowly progressive ptosis and ophthalmoplegia of the extraocular muscles. CPEO may be isolated or associated with other ocular, neurological or systemic disease.
There is no known specific etiology. Most cases of CPEO arise sporadically and are associated with rearrangements (e.g. deletions and duplications) of mitochondrial transfer DNA (mtDNA) segments. There are a few pedigrees with maternal inheritance, suggesting an underlying mtDNA point mutation. Autosomal dominant or recessive inheritance, suggesting underlying nuclear DNA abnormalities, also has been reported. Only recently, mutations in at least three different genes, ANT1 (4q34–35), Twinkle (10q24) and POLG (15q22–26) have been found in patients with autosomal dominant inheritance.
Kearns–Sayre syndrome (KSS) is regarded as a specific and severe form of CPEO, with more signs of mitochondrial disease. Patients with KSS tend to have more mutant mtDNA than individuals with less severe, isolated CPEO. Still, patients with similar phenotypes may have different mtDNA patterns and patients with different clinical presentations may appear to have the same mtDNA rearrangements. Even classical mitochondrial phenotypes without mtDNA mutations have been described.
CPEO is one of the four most common neuro-ophthalmic abnormalities seen in mitochondrial disease. The other three being bilateral optic neuropathy, pigmentary retinopathy and retrochiasmal visual loss. Pathogenic mtDNA mutations are found in at least one in 8000 individuals. There often is only one pathogenic mtDNA deletion involved in mtDNA disease. Maternal age does not seem to influence the incidence of mtDNA deletion disorders. Affected woman were previously thought to have a negligible chance of having clinically affected offspring, but the actual risk is on average about one in 24 births. Heteroplasmy, the co-existence of both mutant and normal mtDNA may play an important role in the variability in clinical expression: Different proportions of mutant mtDNA
(CPEO) Ophthalmoplegia External109 CHAPTERProgressive Chronic •
207
Disorders Neurologic • 12 SECTION
may be present in different tissues in the same person. Still the pathogenesis is only partly understood.
COURSE/PROGNOSIS
The development of ptosis usually proceeds the ophthalmoplegia. Both features usually develop insidiously and symmetrically but can become complete. Patients tend to remain sub-clinical for a long period as most patients experience no diplopia and gradually adjust to ptosis by a chin-up head position and by using the frontalis muscle. Partial sparing of down gaze may contribute to the chin-up head tilt. Ptosis treatment should be undertaken with caution as patients may be prone to develop corneal exposure due to poor Bell’s phenomenon.
DIAGNOSIS
Clinical signs and symptoms
The first symptom of CPEO usually is symmetrical slowly progressive myopathic ptosis. Slowed saccadic velocity can be the first sign of extraocular muscle involvement, and may contribute to the diagnosis in the early stages of the disease. Ptosis and ophthalmoplegia usually develop insidiously and symmetrically and can become complete over time. Pupillary involve-
ment, pain and proptosis are not symptoms of CPEO and warrant further investigation (Figure 109.1).
CPEO is not one distinct diagnosis but a spectrum of diseases ranging from clinically isolated CPEO to symptoms of more widespread mitochondrial disease including myopathy, retinopathy, endocrinopathy, cardiomyopathy, or a combination of symptoms. In 1968, Drachman introduced the term ‘CPEO plus’ for CPEO associated with neurodegenerative disorders.
Kearns–Sayre syndrome (KSS) is characterized by external ophthalmoplegia, pigmentary retinopathy, often referred to as ‘salt and pepper fundus’ and one of either cardiac conduction defect, ataxia or raised CSF protein. KSS typically presents in the second decade of life.
Deafness, and endocrine abnormalities (e.g. hypoparathyreoidism, gonodal dysfunction, and diabetes mellitus) may be present as well. The cardiac conduction defect usually is preceeded by the features of CPEO and can be treated with a pacemaker. Complete heart block resulting in sudden death in these patients, may be associated with long QT syndrome.
Recently, neuropsychological testing in patients with CPEO and KSS revealed specific cognitive deficits suggesting impairment of the visuospatial perception (like visual construction) associated with the parieto-occipital lobes and executive deficits associated to the prefrontal region. No general intellectual deterioration was found. There was no difference in outcome between patients with or without mtDNA deletions.
a |
b |
FIGURE 109.1. a) Notice the ptosis in the left eye. The right eye seems less ptotic but this eyelid is pulled up by a stainless steel crutch attached to the frame. b) In primary position with the eyelids pulled up the left eye is exotropic. c) Attempted upgaze shows restric-
c tion of elevation as a sign of ophthalmoplegia more in the left than in the right eye.
208
Awareness that mitochondrial POLG (polymerase gamma) mutations can underlie parkinsonism is important in patients with CPEO with muscle weakness and neuropathy, as the parkinsonism can be easily masked.
Laboratory findings
The diagnosis must be made on clinical grounds. There is no specific laboratory test for CPEO or KSS. Aim should be focused on ruling out any other underlying disease that could mimic CPEO, like thyroid ophthalmopathy and myasthenia gravis, and on the extent of multisystem involvement in case of mitochondrial disease. Laboratory findings that may aid to the diagnosis are:
●Elevated lactate on serum and CSF measurements as well as on magnetic resonance spectroscopy;
●Elevated pyruvic acid, creatine phosphokinase and aldolase;
●Elevated protein levels in CSF;
●Cytochrome c oxidase deficiency, low magnesium and parathyroid hormone levels also have been reported.
Limb and extraocular muscles of CPEO patients show ragged red fibres on light microscopy using modified Gomori trichrome strain. On electron abnormal paracrystalline inclusion bodies in only some of the muscle fibres, sparing all others, producing ‘selective vacuolization’ have been demonstrated. The selectiveness of the damage resembles that occurring in Leber hereditary optic neuropathy, another mitochondrial disease.
Differential diagnosis
●Neuromuscular junction disease, e.g. myasthenia gravis, botulism.
●Lambert–Eaton syndrome.
●Inflammatory disease, e.g. thyroid associated or idiopathic orbital myositis.
●Neoplasm, primary or metastatic.
●Infiltrative myopathy, e.g. sarcoidosis, amyloidosis.
●Neurologic disorders, e.g. progressive supranuclear palsy.
●Metabolic disease.
Simple and cost-effective tests may be helpful in differentiating CPEO from other diseases:
●The progressive course will rule out congenital deficits;
●Forced duction testing can rule out restrictive myopathies;
●The symmetry of the ophthalmoplegia makes these patients appear to have multidirectional gaze palsies. Full ocular rotations on oculocephalic manoeuvres differentiates supranuclear palsy from CPEO.
PROPHYLAXIS
No effective treatment for mtDNA disorders is available, making prevention important. Informed genetic counseling may be offered.
TREATMENT
Systemic
●Multidisciplinary approach in general, e.g. pacemaker in cases of KSS with serious cardiac conduction defect or heart block.
Ocular
●Adhesive tape or lid crutches for ptosis.
●Lubricants (e.g. artificial tears, gel, ointment).
●Eye patch, goggles and punctum plugs to prevent from exposure keratitis.
●Antibiotic drops or ointment in case of infection and ulceration.
●Fresnelprisms to correct diplopia or head-tilt.
Medical
There is no proven medical therapy. Although various treatments (e.g. coenzyme Q10, riboflavin, ketogenic diets) have anecdotal success.
Surgical
●Levator resection only for ptosis with good levator muscle function.
●Frontalis sling or brow suspension if levator function is poor.
●Diplopia or head-tilt may be corrected with strabismus surgery in which cases muscle resections seem to be more successful than recessions.
●Punctum occlusion can be considered in cases of exposure keratitis.
COMPLICATIONS
Because poor Bell’s phenomenon, these patients are prone to develop corneal exposure from inadequate lid closure due to ptosis treatment, with subsequent exposure keratitis, corneal ulceration and visual loss.
COMMENTS
CPEO is not a specific diagnosis. Mitochondrial DNA mutations, with or without a nuclear-mitochondrial interaction, are increasingly being recognized as the etiology for CPEO and CPEO syndromes.
SUPPORT GROUPS
United Mitochondrial Disease Foundation
P.O. Box 1151
Monroeville, PA 15146-1151
U.S.A.
REFERENCES
Biousse V, Newman NJ: Neuro-ophthalmology of mitochondrial diseases. Current Opinion in Neurology 16(1):35–43, 2003.
Bosbach S, Kornblum C, Schroder R, et al: Executive and visuospatial deficits in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome. Brain 126(Pt 5):1231–1240, 2003.
Carta A, D’Adda T, Carrara F, et al: Ultrastructural analysis of extraocular muscle in chronic progressive external ophthalmoplegia. Arch Ophthalmol 118(10):1441–1445, 2000.
Chinnery PF, DiMauro S, Shanske S, et al: Risk of developing a mitochondrial DNA deletion disorder. Lancet 364(9434):592–596, 2004.
Lee AG, Brazis PW: Chronic progressive external ophthalmoplegia. Current Neurol Neuroscience Reports 2:413–417, 2002.
Luoma P, Melberg A, Rinne JO, et al: Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study. Lancet 364(9437):875–882, 2004.
(CPEO) Ophthalmoplegia External109 CHAPTERProgressive Chronic •
209
Disorders Neurologic • 12 SECTION
Odoari F, Rana M, Broccolini A, et al: Pathogenic role of mtDNA duplications in mitochondrial disease associated with mtDNA deletions. Am J Med Genet A 118(3):247–254, 2003.
Pulkes T, Liolitsa D, Nelson IP, et al: Classical mitochondrial phenotypes without mtDNA mutations; the possible role of nuclear genes. Neurology 61(8):1144–1147, 2003.
Rashid A, Kim MH: Kearns-Sayre syndrome: association with long QT syndrome. J Cardiovasc Electrophysiol 13(2):184–185, 2002.
110 CLUSTER HEADACHE 346.2
(Trigeminal Autonomic Cephalalgia, Cluster Headache Episodic or Chronic,
Horton’s Syndrome, Paroxysmal
Hemicrania, Migrainous Neuralgia,
Histaminic Cephalalgia)
Marijke Wefers Bettink-Remeijer, MD
Rotterdam, The Netherlands
Jan-Tjeerd de Faber, MD,
Rotterdam, The Netherlands
ETIOLOGY/INCIDENCE
Cluster headache is a rare primary headache with an incidence of 1–2 per thousand.
There is a male preponderance, but the male/female ratio is decreasing attributed to a different lifestyle of modern women. (tobacco smoking, alcohol and jobs).
Previously described as a neurovascular disorder, it now seems to be of central origin.
A recent report describes a patient with a complete surgical section of the left trigeminal sensory root who continued to have attacks.
Family studies show an increased risk for first and second degree relatives, but no precise mode of inheritance. Genetic studies suggest an autosomal dominant gene but with low penetrance in some families.
COURSE/PROGNOSIS
Cluster headache usually starts from the second decade to the third and fourth decade.
It has a strong circadian rhythm. It starts often as episodic but can turn into an chronic headache. Patients can have a chronic pattern from onset and some switch from chronic to episodic and vice versa.
Sleep deprivation occurs often, because severe attacks occur often during sleep.
DIAGNOSIS
Clinical signs and symptoms
Cluster headache is a (very) severe unilateral orbital, supraorbital and/or temporal pain lasting if left untreated 15–80 minutes. The headache is accompanied by one or more of the following ipsilateral autonomic signs: conjunctival injection
and/or lacrimation, nasal congestion and/or rhinorrhoe, eyelid oedema, forehead and facial sweating, reversible miosis and ptosis and can be accompanied by a sense of restlessness.
Time between first attack and diagnosis can be very long (1 week to 48 years, median 3 years in one of the studies) 34% had consulted a dentist before diagnosis and 33% a ENT specialist before the diagnosis was established.
Diagnosis is often missed or delayed although circumscript and recognizable criteria are available.
The International Headache Society has put up new criteria.
Paroxysmal hemicrania was previously only recognized as chronic, but has a episodic as well as a chronic form. The main difference with cluster headache is the duration of the attacks and the good reaction to indometacine.
A new entrance in the TACs ( trigeminal autonomic cephalalgias) is SUNCT (short-lasting unilateral neuralgiform headaches with conjunctival injection and tearing).
This syndrome consists of at least 20 attacks of unilateral orbital, supraorbital or temporal stabbing or pulsating pain, lasting 5–240 sec accompanied by conjunctival injection and tearing and occur frequent (3–200 per day).
Differential diagnosis
Structural lesions, as meningeoma and basilar artery aneurysm, have been reported with headache and unilateral autonomic symptoms, but in general clinical symptoms and course make the diagnosis clear. In general, scanning is wise to exclude structural lesions and to reassure the patient and family that there is no other pathological cause for the extreme painful headache.
TREATMENT
Acute attack
Oxygen inhalation and sumatriptan subcutaneous. Oral application is still not effective for aborting attacks. Sham therapy had a higher than expected effect comparing with hyperbaric oxygen sessions.
PROFYLAXIS
Verapamil is the first choice as maintenance prophylaxis, but other agents as lithium, methysergide and valproic acid may be effective as well. Cortisone therapy in a brief tapering course provides temporary relief . Topiramate, gabapentine, naratriptan , melatonine have all been reported effective in trials.
Therapy-resistant cases
Recent reports show effectivity of deep brain stimulation of the hypothalamus. PET scans showed activation of the inferior posterior hypothalamus, stimulation of this region aborts attacks in refractive cases. Cessation of the stimulation brought back the pains.
REFERENCES
Ekbom K, Hardebo JE: Cluster headache: aetiology, diagnosis and management. Drugs 62:61–69, 2002.
International Headache Society guidelines: Online. Available at: www.HIS. org.
210