自99.5.24起,您是第個訪客

    CVA:

1. Infarction (thrombotic & embolic) and hemorrhage

        0.5~1# /qd (keep PT 1.3~1.8 times)

3. About anti-PLTs:

    Low dose aspirin: 100mg/qd

    Watch for provocating gout & GI upset or even bleeding

     Persantin: adj for aspirin

Management of status epilepticus:

Frontotemporal dementia(FTD):

2 Introduction: 10-15% of primary degenerative dementia

Prototypical behavioral disorder arising from frontotemporal cerebral atrophy

How to diagnose？

Clinical diagnostic features (by Lund and Manchester Groups)

    core diagnostic features ：

(A) Behavioural disorders

(I) Insidious onset and slow progression

(II) Early loss of personal awareness

(III) Early loss of social awareness

(IV) Early signs of disinhibition

(V) Mental rigidity and inflexibility

(VI) Hyperorality

(VII) Stereotyped and perservative behaviour

(VIII) Utilisation behavior

(IX) Distractibility, impulsivity and impersistence

(X) Early loss of insight

      (B) Affective symptoms :

                     depression, anxiety, delusion, hypochondriasis, apathy, aspontaneity

        (C) Speech disorder

              (I) Progressive reduction of speech

              (II)Stereotypy of speech

(III) Echolalia and perserveration

(IV) Late mutism

(D) Spatial orientation and praxis preserved

(E) Physical signs

    (I)Early primitive reflexes

     (II)Early incontinence

     (III) Late akinesia, rigidity, tremor

(IV) Low and labile blood pressure

(F) Investigations

(I) Normal EEG

(II)Brain image (structure or functional or both)：predominant frontal or

    anterior temporal abnormality or both                 

(III) Neuropsychology：profound failure on “frontal lobe” test in the absence

    of severe amnesia, aphasia or perceptual spatial disorder

   Supportive diagnostic features

1. Onset before 65
2. Positive FH of similar disorder
3. Bulbar palsy, muscular weakness and wasting, fasciculations (motor neuron disease)

   Diagnostic exclusion features

1. Abrupt onset with ictal events
2. Head trauma related to onset
3. Early severe amnesia
4. Early spatial disorientation
5. Early severe apraxia
6. Logoclonic speech with rapid loss of train of though
7. Myoclonus
8. Cortical bulbar and spinal deficits
9. Cerebellar ataxia
10. Choreoathetosis
11. Early, severe, pathological EEG
12. Brain image：predominantly post-central structural or functional deficit；Multifocal

cerebral lesion

    M. Lab test indicating brain involvement or inflammatory disorder (such as multiple

        sclerosis, syphilis, AIDS and HSV encephalitis) 

Relative diagnostic exclusion features

1. Typical hx of chronic alcoholism
2. Sustained H/T
3. Hx of vascular disease (such as angina, claudication)

Neuropathological diagnostic features :

Pathology：nerve cell loss and spongiform change (microvacuolation) together with mild or moderately severe astrocytic gliosis over frontotemporal regions (unlike AD which showed more significant pathological change over hippocampus & temporoparietal region)

(1) frontal lobe degeneration type

(2) Pick-type (20%)(no senile plaques & neurofibrillary tangles)

(3) Motor neuron disease type

FTD VS AD:

1. disinhibition, aberrant motor behaviors, apathy and euphoria are more significant with FTD (using NPI, plus clinical and SPECT criteria showing accurate rate about 77% on dx FTD)

(Arch Neurol 1996;53:687-690-à by Levy and colleagues)

2. disinhibition is the major behaviour determinant in FTD and delusion is closed associated with AD (using Italian version NPI)

(Arch Neurol 1997;54:350-à by Rozzini and colleagues)

3. H-1 MR spectrometry showed ‾ N-acetylaspartate(neuronal marker) & ‾ glutamate plus glutamine and ­ myoinositol(glial marker) over frontal lobe on FTD, with 92% accurate rate for FTD

(Radiology 1997;203:829-836-à by Ernst and colleagues)

4. MRI alone has only 46% accurate rate for FTD
5. better performance on constructions and calculations in FTD-à even often within normal

   limit ( some argue about the ”constructions” )

   (Neurology 1996；47：1189-1194-à by Cummings and colleagues)

Tolosa-Hunt syndrome:

    Definition: painful ophthalmoplegia due to non-specific granulomatous inflammation in the cavernous sinus

                or superior orbital fissure

    First case reported in 1954 (by Tolosa):

                47 y/o male with severe periorbital pain followed by paralysis of ipsilat. III, IV & VI CN and deminished

                corneal reflex ---> autopsy: low-grade inflammatory process with proliferating fibroblasts, lymphocytes

                & plasma cells in the walls and septa of the cavernous sinus

    Criteria for defining such a syndrome (by Hunt et al):

                (1) "Gnawing" or "boring" periorbital pain occurring before, with, or even after the appearance of an (2)

                ophthalmoplegia due to lesions of CN III, IV, VI. (3) Frequent, but not invariable dysfunction of

                the optic, oculosympathetic, and the first two divisions of CN V. (4) The S/S are seen as a mono-

                phasic illness /c spontaneous remission or recurring after months or years. (5)"Exhaustive" studies

                including angiography and surgical exploration produce no evidance of involving structures outside

                cavernous sinus. (6) Prompt response to steroid therapy.

    Image finding :

                (1) Plain film (if exist)---> Sellar erosion

                (2) Orbital venogram (if exist)---> Obs of the sup ophthalmic v in its 3rd segment /s displacement.

                                                                        Collat. v flow through small v channels or collat. vv.

                                                                        Poor opacification of ipsilat. cavernous sinus

                (3) Arteriography (if exist)---> Displacement or irregular narrowing of siphon portion of ICA

                (4) CT (if exist)---> Convex bowing of lat. wall (infiltration or expansion by a mass)

                                                 Asymm. of two sides or abnormal density within the sinus

                (5) MRI (if exist)---> Cavernous sinus abnormalities (like CT) showing hypointensity relative

                                                        to fat & isointensity with muscle on short TR/TE, isointensity with fat

                                                        on long TR/TE

                                                    Thrombosis of cavernous sinus or sup ophthalmic v

                                                    Resolution of image finding after steroid therapy

    Diagnosis:

                Dx of exclusion was used mostly (Clinic S/S and MRI findings are preferred now)

        << Steroid-responsive ophthalmoplegia: pachymeningitis, chordoma, giant cell tumor

Fetal tissue transplantation in PD (From Current Opinion in Neurology 1998)

    The first successful attempts in 1990, and more than 200 p'ts received this procedure. Multiple

            issues and questions remained unsolved till now.(Is it really effective in reversing PD?)

    Methodological issues of the fetal transplantation procedure:

        (1) The source of fetal tissue:

            * Autologous adrenal medullary transplantation has been abandoned due to failure in many

                multiple clinical trials

            * Elective abortion remain the preferred means (not spontaneous abortion)

            * The entire human ventral mesencephalon is harvested as a donor tissue. (Costanini et al.

                suggested medial ventral mesencephalon from rats' experiments)

            * Experimentation with human neuronal progenitor and stem cells is still in its early stages,

                 but results seem encourging.

        (2) Donor age: 

            * Using tyrosine hydroxylase-like immunoreactivity staining, dopaminergic neurons first

                appear in ventrcular floor at 6 wks of GA. By 8 wks of GA, they started to extend neuritic

                processes which reach the stiatum at 10 wks.

            *  Most investigators agree the optimal time for collecting fetal cells for transplantation is

                6-8 wks of GA for cell suspension and 6-9 wks of GA for solid grafts. 

        (3) Number of donor cells:

            * Complete replacement of the original nigral neurons may not be necessary since clinical

                features of PD don't appear before 60-80% of the nigral neurons and striatal dopamine

                content are lost.

            * Kopyov et al. have demonstrated that p'ts transplanted with a high-volumn sample(24mm³)

                improved significantly than low-volumn sample(20mm³), but this was not a blinded study. 

        (4) Post-transplantation immunosuppression:

            * The need of post-transplantation immunosuppression remains a subject of debate.

            * The need for short-term immunosuppression within the first 6-12 ms post-transplantation

                remains unclear. (probably better with short-term immunosuppression)

        (5) Type of transplant:

            * Two types: cell suspensions and solid grafts

            * Cell suspensions: more even distribution of cells in the target site

            * Solid grafts: easier to prepare and include glial cells which can enhance survival of

                dopamine neurons.

        (6) Site of transplant:

            * The putamen has been the most popular site, because the putamen (esp post. aspect)

                suffers the greatest dopamine deficiency with PD as shown in autopsies or PET studies.

                Besides, microstimulation of the putamen affected more directly the motor behavior of

                rhesus monkeys than the caudate. (Indeed only 12% of human dopaminergic nigral neurons

                project to putamen; therefore, replacing these projections will not compensate enough.)

            * Yet, fetal grafts implanted in the caudate of methylphenyltetrahydropyridine-treated

                monkeys significantly improves motor function.

            * Current clinical data are insufficient to determine the optimum site of implantation.

        (7) Strategies of enhancing viability of the transplanted cells:

            * Neurotrophic factors

            * Free radical scavengers

            * Genetically engineered cell transplant

    Review of clinical trials for fetal tissue transplantation:

        (1) an overall minor to moderate improvement in motor symptoms, but not full reversal

        (2) a prolongation of the ON-state period on L-dopa

        (3) a long-lasting improvement by clinical assessment (up to 5 ys), and by PET scan

                imaging (up to 72 ms).

        (4) restoration of the striatal dopamine in several p'ts by flurodopa PET studies

        (5) prolonged survival of the grafts despite no long term immunosuppression (although

            most of the p'ts who demonstrated grafts survival by PET have received short-term

            immunosuppressant therapy for at least 6 ms.)

        (6) the need for bilat. transplantation

        (7) a fairly low incidence of morbidity and transient adverse events

Mitochondrial myopathy, encephalopathy, lactic acidosis and storke-like episodes:

     Report of a sporadic case and review of the literature(Acta Paed Sin 1994: 35:148-56)

    We studied a 5-year-old boy with mitochondrial myopathy, encephalopathy, lactic

            acidosis and strokelike episodes that are characteristic of the MELAS syndrome.

            Results of biochemical, histopathological, and molecular genetic studies from the

            patient's tissue meet the criteria for diagnosis of mitochondrial disease. An A to G

            transition at the 3243th nucleotide position of mitochondrial DNA (mtDNA) was

            found in the blood cells and hair follicles, instead of in muscle, from the propositus.

            To the best of our knowledge, this is the first reported MELAS case associated

            with mtDNA mutation in blood cells and hair follicles, in stead of in the

            target muscle tissue, that has ever been documented in Taiwan. Brain lesions

            demonstrated by angiography, CT and MRI are discussed.

            (Acta Paed Sin 1994: 35:148-56) 

      In 1984, Pavlakis et al detailed a distinct syndrome, the MELAS syndrome, with

            clinical features of mitochondrial myopathy, encephalopathy, lactic acidosis and

            storke-like episodes

    Point mutation at nt-3243, or 3271 (gene product: tRNA for leucine) in muscle mtDNA

           was found recently. This article emphasized using blood cells as an alternative to

            target muscle tissue in the confirmatory dx of MELAS syndrome.

    Case report:

        5 y/o boy was noted to have episodic vomiting & seizure of r't limbs, with

        learning difficulty, clumsiness & forgetfulness during the prev. 6 ms, and

        dysarthria, r't visual impairment, vomiting, mm weakness, unstable gait, r't side

        weakness & myoclonic seizures during the prev. 3 wks. Height & weight were

        below 5 percentile. L't papilledema, generalized hyporeflexia and uncons. were

        found on day 2. EKG & echo exam were normal. Brain non-contrast CT showed

        hypodensities over l't O-P-T area with mass effect (MRI showed the same lesions).

        EEG revealed asymm. dominance of slow waves over l't hemisphere. brain angio.

        showed early capillary blush instead of arterial occlusion. EMG & NCV were

        normal. ABEP revealed l't sensorineural hearing loss. Hyperlactatemia was noted

        with also increased result in CSF. Histochemical & ultrastructural studies showed

        findings compatible with mitochondrial myopathy. Polarographic & spectro-

        photometric measurements of various enz. activities of mitochondrial indicated

        complex I (NADH-coenz. Q reductase) deficiency in the respiratory chain.

        Restriction enz. analysis revealed a point mutation at the 3243th nucleotide

        position in the mtDNAs of blood cells & hair follicles (No point mutation found

        in p'ts muscle mtDNA). The mutation was also detected, although very low

        level, in the blood cell mtDNA from his mother.

    Tulinius et al proposed the presence of at least 2 of 5 criteria to dx the mitochondrial d's:

         (1) abnormal oximetry

         (2) abnormal spectrophotometry

         (3) histochemical evidence of cytochrome oxidase deficience in the RRF of this case

         (4) point mutation of mtDNA

         (5) abundant ultrastructually abnormal mitochondria

    The most commonly noted CT findings in MELAS are multifocal hypodensities that don't

            correspond to the major cerebrovascular arterial territories (similar characters of decreased

            viability and damage as seen in brain ischemia but preserved circulation of patent vessels

            so-called mitochondrial angiopathy). Upon follow up, cerebral atrophy with dilation of

            the occipital horn was often a prominent feature.

    Morphologic findings of RRF & mitochondrial abnormalities are neither specific nor

            characteristic (not present in all mitochondrial d's)

    Absence of point mutation at either 3243 or 3271 in muscle mtDNA didn't prelude MELAS.

    Clinical features or severity of the d's didn't show correlation with the mutation type. So

            there are some unidentified factors involved in the d's.

    The pathogenesis of hyperlactatemia involves defects of biochemical substrate utilization,

            oxidation-phosphorylation coupling and the respiratory chain. So it may suggest disturbed

            aerobic metabolism in mm and CNS.(lactate more than 16-20 mmol/kg of brain tissue

            will destroy neurons) and is a useful marker for mitochondrial encephalopathies in children

            having s/s in CNS & NM disorders.

    Deficiencies in complex I,II,III,IV& generally decreased enz. activities in the MELAS has

            been reported, and other mitochondrial d's may also have cmplex I defect ---> reliance on

            biochemical analysis to classify the mitochondrial d's can be very confusing.

    Total mtDNAs are greatly increased in RRF (that has strong succinate

       dehydrogenase activity) and the proportion of mutant mtDNA is significantly

        higher in RRF than non-RRF---> mutant mtDNAs are much more abundant in RRF.

        In MELAS, type 2 RRF has more wild-type mtDNA but less COX (cytochrome C

       oxidase) activity comparing with type 2 non-RRF---> increased mutant mtDNAs

        may interfere with mitochondrial function.

   The proportion of mutant to wild-type mtDNAs may be crucial for phenotypic

        expression and for probable threshold effect.

    Increase in the number of mitochondria /c occasional structural abnormalities

       is most prominent in pial arterioles & small arteries up to 250mm in diameter.

        Abnormal proliferation of mitochondria has been seen in smooth mm cells not

       only in brain but also in intramuscular small arteries (demonstrated by SDH

        stain:the proportion of mutant mtDNA is significantly higher in the strongly

        succinate dehydrogenase-reactive blood vessels (SSV) than in non-SSV)--->

        SSV is the major pathologic change related to strokelike episodes.

Etiology of ophthalmoplegia: Retrospective study

    Diplopia and/or ophthalmoplegia are common symptoms of neurological diseases.

        The underlying etiology varies from benign to life-threatening conditions.

        This study tries to perform a retrospective collection of the etiologies of

        ophthalmoplegia. The statistical profile may help clinicians in the assessment

        of patients with ophthalmoplegia.

    Method:

           Medical records of 40 inpatients presented with unknown initial etiologies

        of ophthalmoplegia at National Cheng Kung University Hospital from 1993 to Feb.

        of 1997 were reviewed. Follow-up results were achieved from OPD records or by

        telephone questioning. There were 27 males and 13 females with age ranging

        from 17 to 82 years old. The diagnosis was made by clinical manifestations as

        well as examinations such as computed tomography, magnetic resonance image,

        CSF, erythrocyte sedimentation rate, muscle biopsy, edrophonium test,

        repetitive stimulation test or angiography.  

    Results:

            There are 13 categories of disease entities obtained from our collections of

        total 40 cases: 1.myasthenia gravis(MG) 2.inflammation(Tolosa-Hunt syndrome,

        THS) 3.tumor 4.microvascular lesions (diabetes mellitus or hypertension)

        5.infections 6.demyelinating diseases (Miller Fisher syndrome) 7.cerebro-

        vascular disease 8.aneurysm 9.C-C fistula 10.idiopathic 11.progressive

        external ophthalmoplegia(PEO) 12. trauma 13.undetermined

      ->The definition of idiopathic: single cranial nerve damage with spontaneous

            and good recovery that can‘t be found to have significant causes

      ->The definition of “undetermined”: loss of long enough follow up, receiving

      ->The definition of “THS”: cavernous sinus or superior orbital fissure

      ->The definition of HTN/DM associated microvascular lesions: single cranial

            nerve lesion /c HTN or DM history more than 1 year being bad controlled,

            and no other convincing causes accounting for. 

    Tables of results:

    Discussion:

1) Two age peaks to have ophthalmoplegia are found on our collections: 31~40Y/O

    & more than 61Y/O; hypertension or DM associated microvascular lesions are

    most common during the older group which may be associated with the high

    prevalence during the elders .

2) Generally speaking, undetermined etiology, THS, idiopathic & HTN/DM

    associated causes are more common causes of ophthalmoplegia

3) On our collections, cases with 3,4 & 6th cranial nerve lesion are most common,

   isolated 6th, 3rd, and 4th cranial nerve lesion cases follow. That seems no

    difference from other’s report.

4) During the isolated 3rd cranial nerve lesion cases, DM and/or HTN

   associated  microvascular damage is most, and followed by MG cases—all

   have good prognois.

5) During the isolated 6th cranial nerve lesion cases, idiopathic cause is most,

    and followed by undetermined cases.

     6) If more and enough cases can be collected to achieved a reliable statistical

        profile, maybe the prognosis could be told to the patient according to the

        obtained statistical data---- that may help the clinician much. 

The alien hand syndrome

    Case presentation:

        54 Y/O r't-handed male with lacunar infarct in 1991 leaving the sequelae of r't

    side minimal weakness experienced acute onset of bilat. leg weakness and difficulty

    in speaking, which progressed to partial akinetic mutism over 3 ds. Two CTs were

    performed that showed no marked lesion except brain atrophy. Leg weakness improved

    and he can walk  without support within one month, remaining still r't leg more weak

    than l't leg. MRI performed 5 wks after onset showed compatible with r't ACA

    infarction, involving r't corpus callosum extending from genu to isthmus,

    the r't SMA,anterior cingulate gyrus and medial prefrontal cortex. Abnormal

    movements of 左手 was noticeable 2 wks after onset:例如, 看報紙時,左手會突然翻頁干

    擾閱讀; r't hand把電話筒放回去,而左手反而去拿起來; 左手會自己去抓reachable nearby

    objects with difficulty on releasing; 病人作復健時, 左手抓著sand bag不放, 除非用r't

    hand去扳開左手手指, or耐心勸導左手 to let go; 他常抱怨無法control that “alien hand”

    ,常感沮喪. Also abnormal leg movements were found: 在公園散步時, 一直直走不能改變方向,

    妻子叫他停止, he kept on walking until being interrupted; 有時候, he found himself

    stand still, because his r't leg would not go with l't.若是催促他動, he easily became

    angry and briefly demonstrated a rigid posture, simulating akinesia; 問他想不想上廁所,

    he said no, but went to the nearby toilet immediately.The above bizarre behaviors

    disappeared about 6 ms after the onset.

    Disscussion:

    (1) First described by Brion and Jedynak in 1972 in patients with corpus callosum

        tumors

    (2) Some nouns usually used in alien hand syndrome:

Alien hand sign: a feeling of that one limb is foreign or “ has a will of its own”

    ,together with observable  involuntary motor activity

Personification: treating his “alien hand” as a real person

Magnetic apraxia: affected hand reach out to grasp onto objects within reach, and

    after which voluntary release is difficult

Diagnostic apraxia: abnormal involuntary hand movements elicited by voluntary

    movements of the other hand

Intermanual conflict: one hand involuntarily (not triggered by the other hand)

    conflict with the other hand

Mirror movement: one hand involuntarily mimics the other

Autocriticism: patient critical of his limb’s action

Self-restriction: attempt to control the alien hand with the other hand by forcibly

    restraining the affected hand

      Compulsive manipulation of tools (CMT): unilateral involuntarily handling and

           utilization of familiar objects  

    (3) Alien hand sign is often associated with:

        frontal stroke, corpus callosum infarct, A-com artery rupture, bifrontal

        penetrating cerebral injury, combination of posterior corpus callosum lesion

        & contralateral thalamic sensory lesion, and corticobasal ganglionic

        degeneration etc.

    (4) DD with the alien hand sign:

        grasp reflex, athetosis, pseudoathetosis, action dystonia, hemiballismus,

        hemiataxia, seizure originally from SMA, and neglect syndrome etc.

    (5) Two alien hand syndromes were reported:

     Callosal type: involving only corpus callosum—presenting with intermanual

     conflict & other disconnection syndrome by the non-dominant hand (possible

     mechanism: a failure of medial frontal transcortical inhibition of the non-

     dominant hemisphere during tasks requiring dominant-hemisphere motor control

     or verbal mediation.) 

Delayed Syrinx Formation after Tuberculous Meningitis: Report of a Case (by

        Ing-Jer Huang, Tzu-Tung Tsai)

    Even though the relative effective anti-tuberculous drugs have been

        TB meningitis.

    Case report:

        and was thought to be a late complication of previous TB meningitis.

          Due to the cystic component within the cord with separations, drainage

    Discussion:

The absence epilepsies

    Summary:  Four syndromes comprise the absence epilepsies. Each is classically

        associated with the absence seizure, although other syndromes also have

        absence attacks as part of their repertoire. The most common syndrome is

        childhood absence epilepsy; it usually occurs in the age range of 6-7 ys.

        The absence seizures may occur many times daily, and EEG characteristics

        are the most typical of the absence epilepsies. The second form of absence

        epilepsies is juvenile absence epilepsies; it begins near puberty and may

        represent a continuum from the childhood form. Myoclonic seizures are more

        common than in the childhood form, and the spike-wave discharges in the

        EEG are often faster than that seen in childhood absence epilepsies. The

        3rd form of absence epilepsy is juvenile myoclonic epilepsy characterized

        especially by myoclonic jerks in the morning; these attacks occasionally

        progress to generalized tonic-clonic seizures. The final form of absence

        epilepsy is epilepsy with myoclonic absences, a rare disorder with a

        specific form of absence seizures. The absence seizure itself is observed

        to a greater or lesser extent in all of these syndromes. This seizure is a

        curious event, and its causes are poorly explained by current knowledge of

        the fundamental mechanism of the epilepsies. Although the etiology of the

        absence seizure at a biochemical level is unknown, some studies suggest

        that certain low-threshold calcium ion currents (T current) which are

        partially controlled by GABA-B mechanisms, may activate burst firing of

        thalamic neurons, initiating an absence seizure. The evidence of a genetic

        predisposition for the absence epilepsies is overwhelming. Although the

        nature of genetic abnormalities remains unclear, promising investigations

        may soon reveal the location and the nature of the genetic defect.

      Poupart (1705, cited in Temkin, 1971) provided the first good description

        of the seizures: At the approach of an attack the patient would sit down

        in a chair, her eyes open, and would remain there immobile and would not

        afterward remember falling into this state. If she had begun to talk and

        the attack interrupted her, she took it up again at precisely the point

        at which she stopped and she believed she had talked continuously.

      Distinction between absence and CPS

           Absence: Duration typically 5-15 s

                     Usually rudimentary if occur       

                 Immediate return of cons.                

                 P‘t feel normal after attack   

                 Not preceded by any other seizure

                 Typical 3-Hz spike-and-wave

                 To ethosuximide & VPA 

    Features of absence seizures (from Penry et al 1975 & Porter 1989):

        Very rarely longer than 45 s, ordinarily lasting less than 10 s

      Not assoc. /c auras,postictal abnormalities,hallucinations,formed speech

      Absence and atypical absence seizures:

        (1) By Holmes et al 1987: p't with atypical absence may have a much higher

        likelihood of having developmental delay, other seizure types, and EEG

        with interictal abnormalities; also typified by more prominent increases

        or decreases in mm tone; automatisms were found in 44% of typical & 22%

        of atypical absence seizures;onset & cessation were abrupt in each type

        (2) By Basim 1993 : atypical absence evolves gradually, terminates abruptly

        with different EEG types as follows-- 1) diffuse irregular spike wave at

        2-2.5 Hz with or without fragmentation (cons. was regained during

        fragmentation or when spike wave discharges were < 2 Hz) 2) irregular

        diffuse fast activity at 10-13 Hz 3) a combination of fast spike wave or

        sharp waves of increasing amplitude followed by synchronous spike wave

        discharges at 3 Hz

      Favorable prognosis:

        Sato et al 1983 : normal or above-average intelligence, normal NE, male,

        lack of hyperventilation-induced spike-waves on EEG

      EEG characteristics of absence

      Gomez and Westmoreland 1987 : generalized, bilaterally synchronous,

        regular, stereotyped and symmetrical 3-Hz spike and wave complexes with

        an abrupt onset & end (hyperventilation was the most effective activator)

    Clinical syndromes of absence

        most common; 6-7 y/o; girls more; may many times daily (even > 100); cons.

        is severely impaired but opening eyes with retaining reflex response to

        visual threat, pain & sometimes auditory stimuli; associated GTC may be

        present; typical EEG of absence

        begin near puberty; sex equally; absence seizures less but myoclonic more

        than childhood type; similar pictures as childhood form but milder that

        makes some awareness & recollection of ictal events possibly preserved

        (almost closing eyes); EEG change similar to childhood form but often

        faster than 3 Hz

        myoclonic jerks usually after awaking affecting one arm; sex equally;

        15 y/o about; much less impaired cons. (adolescent p‘t may continue his

        activity even mathematical calculations & speech, and even comprehension

        of speech is intact); almost closing eyes; rare automatism; spike-

        multispike-slow waves complex is not rhythmic, and ictal discharge

        fragmentations & spike-wave discharges look like “worm” or compressed Ws

        rare; stereotyped absence attacks with severe bilat. rhythmic clonic

        jerking, typically of outstretched, semiflexed arms; boys more; 7 y/o about;

        usually mental deterioration and therapy resistant; rhythmical myoclonic

        jerks at 3-Hz making dx unmistakable

      Genetic factors in absence epilepsy: multifactorial inheritance or single AD

        ...... unclear

      Therapy

        (1) Ethosuximide is the drug of choice, although VPA should be used first

            if concomitant GTCs are present

  (2) Effective plasma level of ethosuximide: 60-100m g/ml

                                                 VPA : 50-100m g/ml

                VPA : GI upset, hair loss, weight gain, tremor, hepatotoxicity 

Adrenoleukodystrophy

        Summary:

               The main advances concerning adrenoleukodystrophy have been in the fields

        of genetics and therapy. Abnormalities in the ‘putative gene’ reported

        in 1993 have been confirmed. Mutations in this gene have been demonstrated

        in all of the 80 adrenoleukodystrophy families studied so far in various

        parts of the world. The same unusual dinucleotide deletions were present

        in approximately 20% of families. The remaining deletions involved nearly

        all parts of the gene and in most instances were unique in each family.

        There was no correlation between the phenotype and the nature or location

        of the mutation. Follow-up of patients treated with Lorenzo's Oil suggests

        that this therapy does not alter the course of the illness in symptomatic

        patients. However, dietary therapy started before the development of

        symptoms may reduce the frequency and severity of subsequent neurological

        disability.

    Content:

            (1) X-linked (Xq28), mainly affect the nervous system white matter, adrenal

            cortex and testis

        (2) The principal biochemical abnormality: accumulation in tissues and body

            fluids of saturated unbranched very long chain fatty acids (VLCFA),

            due to impaired capacity to degrade these substances (normally occur

            in the peroxisome)

        (3) Clinical manifestations are variable:

                i. Childhood cerebral form: boys develop normally until 4~8y/o; early

                symptoms usually are mistaken to be “attention deficit disorders”

                ; impaired auditory discrimination, visual disturbance, impaired

                coordination, dementia or seizure; progress rapidly, may lead to

                an apparently vegetative state within 2 ys, and to death at any

                time thereafter; 90% exist primary adrenocortical insufficiency

                ii. Adrenomyeloneuropathy: most commonly in the 3rd decade; paraparesis

                and sphincter disturbance due to a ‘dying back’ degeneration of

                the long tract in the spinal cord; progress over decades and is

                often misdiagnosed as multiple sclerosis; 70% exist primary

                adrenocortical insufficiency

                iii. Adolescent cerebral and adult cerebral form: like childhood

                cerebral form

                iv. Addison-only form: nervous system appears to be spared (many, but

                not all,of these p'ts later develop signs of adrenomyeloneuropathy)

                v. 20% of women heterozygous for adrenoleukodystrophy develop a

                syndrome resembling Adrenomyeloneuropathy with somewhat milder and

                later onset, remaining normal adrenal function

    Diagnosis: clinical features combine with increased level of saturated

        VLCFA in plasma. Brain MRI that may reveal symmetrical demyelinating

        lesions in the parieto-occipital region are often helpful.(but unilateral

        lesion is still possible)

    The various forms of adrenoleukodystrophy often occur within the same

        kindred or nuclear family-à an autosomal modifier gene is the most likely

        explanation for the wide range of phenotypic expression

    Unusual phenotypes: i. Presentation resembling OPCA in adults (particularly

                                in Japan)

                                                    ii. Presentation resembling OPCA in children

                                        iii. A Scottish family have 3 brothers presenting with

                                typical symptoms of adult cerebral form

                                adrenoleukodystrophy (most families show a wide range

                                of intrafamilial phentypic variability

    Up to now the known false-negative results of VLCFA in heterozygotes have

        made it impossible to exclude carrier status. However, in families where

        the primary defect has been defined in a male proband, demonstration that

        a female relative does not carry this mutation will make it possible to

        exclude carrier status with a high degree of certainty.

    Therapeutic evaluations:

            (1) Results of Lorenzo's Oil therapy started before there are neurological

            symptom are encouraging. So it's recommended all men with Addison d's

            be tested for adrenoleukodystrophy.

            (2) It’s recommended all asymptomatic relatives who are at genetic risk

            of adrenoleukodystrophy, as well as all male p'ts with Addison d's, be

            screened for adrenoleukodystrophy, and be urged to join one of the

            international protocols designed to evaluate the effectiveness of this

            therapy