Online newspaper of professor Yasser Metwally

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

May 29, 2009 — Epilepsy is a chronic disorder of the brain characterized by recurrent seizures, as opposed to seizures occurring in association with high fever, drug effects, chemical imbalance (e.g., low blood sugar). Epilepsy can occur without other evidence of neurologic dysfunction, but it is often associated with more global neurologic abnormalities, such as autism, cerebral palsy, or mental retardation.

The majority of autistic persons do not have seizures. However, they are at higher risk for seizures if they have certain specific neurologic conditions, such as tuberous sclerosis, neurofibromatosis, untreated phenylketonuria.

Infantile spasms (sudden generalized muscle contractions, usually beginning between ages 3 and 8 months) do occur in association with autism, often in young children who have tuberous sclerosis or other significant neurologic problems. Other forms of epilepsy–complex partial epilepsy, generalized tonic-clonic epilepsy and, more rarely, absence seizures–also may occur in autistic children. The frequency of epilepsy in autistic children is below 15% (my estimate) and, if seizures do occur, they are more likely to occur in the autistic child who is also mentally retarded.

There is an increased incidence of seizures in otherwise seizure-free autistic persons when they become adolescents. Roughly 25-30% of autistic adolescents have been reported to develop seizures, although such a high incidence has not been noted by me. It is of note that the seizures are usually not serious, are usually controlled by anticonvulsants, and are inclined to diminish in adulthood. The reason for this significant increased frequency of seizures in autistic adolescents is unknown and may represent, at least in part, the general tendency for seizure disorders to become more problematic at puberty.

Clinical presentation

There are many autistic persons who have behavior and mannerisms, e.g., swaying, sudden repetitive movements, which may raise questions about a seizure disorder. This is a valid concern because seizures can reduce one’s awareness of the environment and/or create anxiety and thus enhance autistic behavior and communication problems. How can seizures be distinguished from unusual behaviors?

Video 1. Stereotyped behavior in an autistic patient

1. Seizures are sudden and without provoking events. If an autistic person’s suspected “seizures” are clearly the consequence of anger, frustration, fear, these episodes are probably not seizures. (On occasion, seizures are provoked by certain light frequencies or sounds. Seizures can also be brought on by prolonged hyperventilation in a person susceptible to seizures.)

2. Seizures generally follow a similar -pattern each time, although some seizures might be more intense and prolonged than others. If the autistic person’s “seizures” are varied in movements and mannerisms, these events are probably not seizures.

3. Generalized seizures are often associated with an aura (perhaps a sense of fear or odd sensations) and may be followed by a headache, weakness or exhaustion. If the autistic person has had a major “seizure,” it is unlikely he would immediately resume his regular activity.

4. Absence attacks, often suggested by the autistic person’s staring mannerisms, involve brief (less than 10 seconds unless frequent episodes) loss of consciousness, often with some eyeblinking or mild facial movements. Complex partial seizures, which can also involve staring, are also often associated with some associated movements, lip-smacking, shuddering. If an autistic person has frequent staring episodes, it is important to determine if there is any response to environmental stimuli and whether there are any associated movements.

Figure 1. Autistic children

Diagnostic Studies

If there is any question about repeated, unpredictable and similar episodes of unusual behavior and/or movements, an electroencephalogram (EEG) should be done. A sleep EEG is usually the most productive. Obtaining an EEG in the autistic population can require patience, creative scheduling, and sedation. An EEG is done to help localize the origin of the abnormal electrical activity in the brain and can help determine the most appropriate therapy. Other diagnostic studies might be necessary. An MRI or CT would be done to rule out a brain tumor or malformation. Blood studies would be done to rule out metabolic disturbances. In very puzzling cases, EEG telemetry might be used. 

Seizure Treatment

If the EEG supports the clinical diagnosis of a seizure disorder or if the clinical history is strongly suggestive but an EEG is unobtainable, anticonvulsant therapy should be considered. Carbamazepine (Tegretol) and valproic acid (Depakene) are the most commonly used anticonvulsants. They have relatively few significant side effects, and often have positive behavioral effects–the improved behaviors may not relate to seizure control. There are a variety of other traditional anticonvulsants, including phenobarbital, diphenylhydantoin (Dilantin), and ethosuximide (Zarontin). Barbiturates often make children more hyperactive and irritable, and diphenylhydantoin has a range of subtle metabolic, endocrinologic, and neurologic side effects. There are also a variety of newer anticonvulsants (vigabatrin, lamotrigine, gabapentin) which hold promise.

It is important to note that all anticonvulsants may have behavioral and cognitive side effects. Therefore, anticonvulsant therapy needs to be carefully monitored and probably not considered in a person with rare, brief and/or questionable seizures.

Landau-Kleffner Syndrome

This syndrome was first described in 1957 and is also known as acquired epileptic aphasia. By definition, this condition affects children, usually between the ages of 3 and 7, who previously had no developmental, language, or interactional difficulties. They usually experience a rather abrupt loss of language comprehension and a diminution in their ability to express themselves. They usually have clear-cut seizures. Their EEG, especially their sleep EEG, is abnormal.

Children with Landau-Kleffner syndrome do not necessarily appear autistic, although the quick loss of language comprehension and the resultant communication handicap could certainly cause significant confusion and frustration. Some affected children therefore might appear autistic.

If anticonvulsant therapy is given, the seizures often cease and the EEG improves. The aphasia may also resolve, although this is less predictable. The cause for the aphasia in Landau-Kleffner syndrome is still uncertain. The seizures and the aphasia may both reflect abnormal brain functioning (due to inflammation, growths, unknown structural or neurochemical abnormalities) or the aphasia may be a consequence of the seizure discharges.

The treatments for Landau-Kleffner syndrome are primarily speech/language therapy and anticonvulsants. Corticosteroid therapy and neurosurgery have also yielded some positive results.

It would be rare for an autistic person to have Landau-Kleffner syndrome, since this syndrome denotes an aphasia, usually acquired after the age of 2-3 in a previously normally developing child. The onset of the aphasia (diminished understanding of language) should roughly coincide with the onset of seizures. If seizures are not obvious, the EEG should be abnormal.

If there are concerns about Landau-Kleffner syndrome in a child suspected of being autistic, a sleep EEG should be obtained. If the EEG is normal, Landau-Kleffner syndrome is highly unlikely. However, there could be some confusion if the EEG is obtained several years after the onset of the aphasia; according to Dr. Gerry Stefanatos (see below), the EEG may spontaneously normalize, although the aphasia persists. LandauKleffner syndrome could still be diagnosed in the absence of an abnormal EEG; specialized studies are necessary and include use of the SPECT (single photon emission CT) and a modification of the auditory evoked response procedure.

Video 2. Seizures in Children with Autism Disorders

References

1. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 10.1a January 2009 [Click to have a look at the home page]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

May 24, 2009 — Parkinson’s disease (PD) is an age-related, progressive neurodegenerative disorder initially characterized by resting tremor, rigidity, or bradykinesia 1. Cognitive changes can complicate the long-term management of PD and are estimated to occur in 20% to 40% of all diagnosed patients who have PD, leading to a diagnosis of Parkinson’s disease with dementia (PDD). Alternatively, dementia may precede or may occur concomitantly with the onset of motor symptoms, suggesting a diagnosis of dementia with Lewy bodies (DLB). Excellent reviews have been published illustrating the effects of dementia as a complication of PD (ie, PDD) or possibly as a separate entity (DLB) [2–13]. Regardless of the specific classification of cognitive impairment accompanying the extrapyramidal features of PD, dementia has a great impact on the course and management of PD symptomatology. This review is designed to highlight the difficulty in distinguishing PDD from DLB and to discuss current management strategies.

Video 1. Parkinson’s Disease Dementia

• Risk and consequences of dementia complicating Parkinson’s disease

The long-term risk of developing dementia as a consequence of PD is controversial. In one longitudinal study, 20% of patients who had PD developed dementia during a 10-year follow-up 14. In this study, none of the age-matched controls met clinical criteria for dementia during the follow-up period. In another study, patients diagnosed with PD were followed prospectively for the development of dementia for an average of 8 years. Results showed 4-year and 8-year prevalence rates of dementia of 51.6% and 78.2%, respectively, compared with a 5-year prevalence rate of only 18.5% among patients who did not have PD 15. Unfortunately, in this study, a large number of subjects failed to complete the trial, and those who completed the study had a higher incidence of cognitive impairment at baseline compared with noncompleters. In addition, a high proportion (26%) of subjects had dementia at their baseline evaluation. Another study suggests that more than 65% of patients who have PD and are at least 85 years of age are demented, with a particularly steep increase in risk occurring between ages 65 and 75 16. Deficits in recall of verbal material, set formation, cognitive sequencing, language expression, and semantic fluency are detected in patients who have disease durations as short as 16 months 17. Advanced age (onset in the 8th decade) and severity of disease combined also may play a role, increasing the risk of developing dementia by almost tenfold in one prospective cohort study compared with younger (onset in the 6th decade) or less severe clinical presentations of PD in the elderly 18. In this study, almost 30% of all patients developed dementia over an average follow-up period of 3.6 years. Estimates of the actual risk of developing dementia in PD range from 2.7% to 9.5% per year 19.

The incidence and prevalence of DLB also is difficult to assess. In an older review of articles examining dementia as a complication of PD, Cummings found an overall prevalence of 40% in 27 studies representing more than 4300 patients 20. Almost all of the studies used neuropsychologic measures to define dementia; however, pathologic features of dementia associated with Alzheimer’s disease (AD) were noted in some postmortem examinations. Because of the lack of autopsy-proven diagnoses and the absence of specific immunohistochemical markers for cortical Lewy bodies, the prevalence rates probably included cases of PDD and DLB. Recent hospital-based autopsy studies suggest that DLB accounts for 15% to 25% of all dementia cases 21. Clinicopathologic studies demonstrate significant overlap between different disease entities, such as PDD, DLB, and AD (see later discussion) [22–27].

Regardless of the exact clinical entity, the coexistence of dementia with parkinsonian features is associated with accelerated debilitation and shortened lifespan. In a 3-year longitudinal study of 114 patients who had three different types of dementia—AD, DLB, and vascular—there was no significant difference in the age of onset, age at death, or overall survival 28. In another study comparing 185 patients who had definite AD and 60 patients who had autopsy-confirmed AD plus Lewy bodies, cognitive and functional decline and survival were similar 29. A 5-year observational study of 250 patients who had PDD versus PD showed a slight but significant shortening of lifespan with PDD, although later age at onset of PD symptoms correlated with the shortest lifespan 3. In perhaps the most comprehensive study to date, Levy and colleagues followed 180 patients who had idiopathic PD without dementia for a mean follow-up period of 3.9 years 30. During that time, 41 of the patients died, 49% (20 of 41) of whom had developed dementia compared with the development of dementia in 23% (32 of 139) of subjects who remained alive 30. The conclusions of this study suggest that dementia was an independent variable for death and increased mortality. When the investigators controlled for the severity of motor symptoms, the risk of death was increased twofold.

• Etiology of Parkinson’s disease with dementia and dementia with Lewy bodies

Motor impairment in PD is considered the result of selective degeneration of dopamine-producing neurons in the zona compacta of the substantia nigra 31. Two distinct neuronal inclusions are observed in nondemented idiopathic PD. The hallmark neuropathologic feature of PD is the presence of Lewy bodies in the substantia nigra 32. Lewy bodies are composed of abnormally phosphorylated neurofilament proteins aggregated with ubiquitin and large amounts of nitrated a-synuclein, a protein normally present at neuronal synapses that may be involved in synaptic vesicle release [33,34]. Postmortem observations suggest that Lewy body biogenesis may be related to defects in protein clearance, resulting in protein aggregation into Lewy bodies and resistance to normal proteasomal activities 35. It seems unlikely, however, that global deficits in brain proteasomal function exacerbate aggregation 36. A second neuronal inclusion, the pale body, is restricted in distribution to the substantia nigra and locus coeruleus 32. The involvement of the locus coeruleus suggests a more significant role for this noradrenergic nucleus in the neuropathophysiology of PD. Recent postmortem studies document significant neuronal loss in the locus coeruleus in cases of PD 37, implying an additional neurochemical alteration in this neurodegenerative disease.

The etiology of dementia in PDD and DLB is complicated. Recent advances in immunostaining techniques have led to the identification of widespread Lewy bodies in the cerebral cortex and brainstem of demented parkinsonian patients [38,39]. An autopsy study that examined the brains of 22 demented and 20 nondemented patients who had a clinical and neuropathologic diagnosis of PD found large numbers of a-synuclein–positive cortical Lewy bodies in 91% of patients who had dementia, compared with only 10% of patients who did not have dementia. The results suggest that Lewy body neuropathic changes are the primary histopathologic correlate of dementia in PD 27.

AD-type pathology, including neuritic plaques and neurofibrillary tangles, also is observed in patients who have PD with dementia. In one study, neuropathologic signs of AD were found in 17 of 100 cases of PD 40. A recent autopsy series of 13 patients who had PD and late-onset dementia found a trend toward increased neuritic plaque and neurofibrillary tangle counts in the neocortex, the CA1 region of the hippocampus, and the entorhinal cortex 19. Moreover, Lewy body counts were correlated with the number of senile plaques and neurofibrillary tangles 19. In more than half of patients who had PDD and late-onset dementia, Lewy bodies were found restricted to limbic areas with only sparse involvement of the neocortex (referred to as transitional or intermediate Lewy body disease), compared with patients who had diffuse cortical Lewy body disease where the neocortex also was involved 19. A later study found no significant relation between the deposition of amyloid ß-peptide, a component of AD plaques, and Lewy body counts 41. The investigators of this study concluded that the presence of PD with neuropathologic signs of AD was purely coincidental; however, they suggested that synergies between PD and AD pathologies may contribute to dementia.

Together, these data suggest that dementia in patients who have PD may occupy an intermediate therapeutic space between pure PD and pure AD, with elements of both pathologic processes potentially contributing to the development of dementia. Whatever the cause of dementia, Lewy body inclusions seem to predict severity of cognitive deficits in the elderly patient who has PD. A study of brain specimens from 273 elderly subjects referred from a long-term care facility found a significant correlation between the presence and density of Lewy body inclusions and the degree of dementia in multiple brain regions, both in patients who had definitive clinical AD diagnoses and in patients who had non-AD dementia 42.

• Clinical, neuropsychologic, and imaging characteristics of Parkinson’s disease with dementia and dementia with Lewy bodies

There is controversy about whether or not PDD and DLB are separate clinical entities or part of a continuum of disease 2. Tentative clinical distinctions are made between the two diseases. Patients presenting initially in the absence of cognitive decline over the previous 12 months and with characteristic motor symptoms, including resting tremor, bradykinesia, or rigidity, generally qualify for a presumptive diagnosis of idiopathic PD. If dementia develops more than 1 year after the onset of motor symptoms, the dementia is given the designation of PDD. Patients presenting initially with dementia with concomitant or somewhat later onset of extrapyramidal features commonly are assigned a diagnosis of DLB. Although consensus criteria are established for the diagnosis of DLB, it is unclear if PDD and DLB are indeed discrete. In an autopsy-confirmed series, pathologically confirmed cases of DLB had a greater than 80% chance of presenting initially, with features of dementia, whereas extrapyramidal features initially were present in only 43% of patients 43. A small number of these patients presents with parkinsonism alone, other psychiatric disorders without dementia, orthostatic hypotension, falls, or transient disturbances in consciousness 43. For a diagnosis of probable DLB, consensus guidelines developed by the Consortium on Dementia with Lewy Bodies require the presence of dementia plus at least two of the following core features: fluctuating cognition and levels of consciousness, the presence of visual hallucinations, or the motor features of parkinsonism. Features supportive of the diagnosis include repeated falls, syncope, transient loss of consciousness, neuroleptic sensitivity, systematized delusions, and hallucinations 21. A diagnosis of possible DLB requires only one of these core features accompanying the dementia. A study conducted by Richard and colleagues suggests that time to clinical feature onset may be helpful for distinguishing between PDD and DLB (Table 1) 2. Unfortunately, the pathologic features of these two disease entities demonstrate significant overlap (see previous discussion).

Table 1. Clinical features that may distinguish Parkinson’s disease, Parkinson’s disease with dementia, and dementia with Lewy bodies

Data from a study of 66 cases with neuropathologic evidence of Lewy bodies with minimal AD changes (Richard IH, Papka M, Rubio A, Kurlan R. Parkinson’s disease and dementia with Lewy bodies: one disease or two? Mov Disord 2002;17:1161-;5).

References

1. Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson disease. Arch Neurol. 1999;56:33–39.

2. Richard IH, Papka M, Rubio A, Kurlan R. Parkinson’s disease and dementia with Lewy bodies: one disease or two?. Mov Disord. 2002;17:1161–1165.

3. Nussbaum M, Treves TA, Inzelberg R, Rabey JM, Korczyn AD. Survival in Parkinson’s disease: the effect of dementia. Pakinsonism Relat Disord. 1998;4:179–181.

4. Emre M. Dementia associated with Parkinson’s disease. Lancet Neurol. 2003;2:229–237.

5. Emre M. What causes mental dysfunction in Parkinson’s disease?. Mov Disord. 2003;18:S63–S71.

6. McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen-Mansfield J, et al.. Dementia with Lewy bodies. Lancet Neurol. 2004;3:19–28.

7. Waters CH. Treatment of advanced stage patients with Parkinson’s disease. Parkinsonism Relat Disord. 2002;9:15–21.

8. Rabinstein AA, Shulman LM. Management of behavioral and psychiatric problems in Parkinson’s disease. Parkinsonism Relat Disord. 2001;7:41–50.

9. Wolters EC. Intrinsic and extrinsic psychosis in Parkinson’s disease. J Neurol. 2001;248(Suppl 3):III-22–III-27.

10. Noe E, Marder K, Bell KL, Jacobs DM, Manly JJ, Stern Y. Comparison of dementia with Lewy bodies to Alzheimer’s disease and Parkinson’s disease with dementia. Mov Disord. 2004;19:60–67.

11. Iseki E. Dementia with Lewy bodies: reclassification of pathological subtypes and boundary with Parkinson’s disease or Alzheimer’s disease. Neuropathology. 2004;24:72–78.

12. Korczyn AD. Dementia in Parkinson’s disease. J Neurol. 2001;248(Suppl 3):III-1–III-4.

13. Poewe W. Psychosis in Parkinson’s disease. Mov Disord. 2003;18(Suppl 6):S80–S87.

14. [14]Hughes TA, Ross HF, Musa S, Bhattacherjee S, Nathan RN, Mindham RH, et al.. A 10-year study of the incidence of and factors predicting dementia in Parkinson’s disease. Neurology. 2000;54:1596–1602.

15. Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sørensen P. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol. 2003;60:387–392.

16. Mayeux R, Chen J, Mirabello E, Marder K, Bell K, Dooneief G, et al.. An estimate of the incidence of dementia in idiopathic Parkinson’s disease. Neurology. 1990;40:1513–1517.

17. Cooper JA, Sagar HJ, Jordan N, Harvey NS, Sullivan EV. Cognitive impairment in early, untreated Parkinson’s disease and its relationship to motor disability. Brain. 1991;114:2095–2122.

18. Levy G, Schupf N, Tang MX, Cote LJ, Louis ED, Mejia H, et al.. Combined effect of age and severity on the risk of dementia in Parkinson’s disease. Ann Neurol. 2002;51:722–729.

19. Apaydin H, Ahlskog JE, Parisi JE, Boeve BF, Dickson DW. Parkinson disease neuropathology: later-developing dementia and loss of the levodopa response. Arch Neurol. 2002;59:102–112.

20. Cummings JL. Intellectual impairment in Parkinson’s disease: clinical, pathologic, and biochemical correlates. J Geriatr Psychiatry Neurol. 1988;1:24–36.

21. McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, et al.. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology. 1996;47:1113–1124.

22. Mattila KM, Rinne JO, Roytta M, Laippala P, Pietila T, Kalimo H, et al.. Dipeptidyl carboxypeptidase 1 (DCP1) and butyrylcholinesterase (BCHE) gene interactions with the apolipoprotein E epsilon4 allele as risk factors in Alzheimer’s disease and in Parkinson’s disease with coexisting Alzheimer pathology. J Med Genet. 2000;37:766–770.

23. Trembath Y, Rosenberg C, Ervin JF, Schmechel DE, Gaskell P, Pericak-Vance M, et al.. Lewy body pathology is a frequent co-pathology in familial Alzheimer’s disease. Acta Neuropathol (Berl). 2003;105:484–488.

24. Jellinger KA, Seppi K, Wenning GK, Poewe W. Impact of coexistent Alzheimer pathology on the natural history of Parkinson’s disease. J Neural Transm. 2002;109:329–339.

25. Harding AJ, Halliday GM. Cortical Lewy body pathology in the diagnosis of dementia. Acta Neuropathol (Berl). 2001;102:355–363.

26. Londos E, Passant U, Gustafson L, Brun A. Neuropathological correlates to clinically defined dementia with Lewy bodies. Int J Geriatr Psychiatry. 2001;16:667–669.

27. Hurtig HI, Trojanowski JQ, Galvin J, Ewbank D, Schmidt ML, Lee VM-Y, et al.. Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson’s disease. Neurology. 2000;54:1916–1921.

28. Walker Z, Allen RL, Shergill S, Mullan E, Katona CL. Three years survival in patients with a clinical diagnosis of dementia with Lewy bodies. Int J Geriatr Psychiatry. 2000;15:267–273.

29. Lopez OL, Hamilton RL, Becker JT, Wisniewski S, Kaufer DI, DeKosky ST. Severity of cognitive impairment and the clinical diagnosis of AD with Lewy bodies. Neurology. 2000;54:1780–1787.

30. Levy G, Tang M-X, Louis ED, Cote LJ, Alfaro B, Mejia MA, et al.. The association of incident dementia with mortality in PD. Neurology. 2002;59:1708–1713.

31. Greenfield JG, Bosanquet FD. The brain stem lesions in parkinsonism. J Neurol Neurosurg Psychiatry. 1953;16:213–226.

32. Gibb WRG, Scott T, Lees AJ. Neuronal inclusions of Parkinson’s disease. Mov Disord. 1991;6:2–11.

33. Duda JE, Giasson BI, Chen Q, Gur TL, Hurtig HI, Stern MB, et al.. Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies. Am J Pathol. 2000;157:1439–1445.

34. Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M. a-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proc Natl Acad Sci U S A. 1998;95:6469–6473.

35. McNaught KS, Shashidharan P, Perl DP, Jenner P, Olanow CW. Aggresome-related biogenesis of Lewy bodies. Eur J Neurosci. 2002;16:2136–2148.

36. Furukawa Y, Vigouroux S, Wong H, Guttman M, Rajput AH, Ang L, et al.. Brain proteasomal function in sporadic Parkinson’s disease and related disorders. Ann Neurol. 2002;51:779–782.

37. Zarow C, Lyness SA, Mortimer JA, Chui HC. Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch Neurol. 2003;60:337–341.

38. Hansen L, Salmon D, Galasko D, Masliah E, Katzman R, DeTeresa R, et al.. The Lewy body variant of Alzheimer’s disease: a clinical and pathologic entity. Neurology. 1990;40:1–8.

39. Lennox G, Lowe J, Morrell K, Landon M, Mayer RJ. Anti-ubiquitin immunocytochemistry is more sensitive than conventional techniques in the detection of diffuse Lewy body disease. J Neurol Neurosurg Psychiatry. 1989;52:67–71.

40. Hughes AJ, Daniel SE, Blankson S, Lees AJ. A clinicopathologic study of 100 cases of Parkinson’s disease. Arch Neurol. 1993;50:140–148.

41. Jendroska K, Lees AJ, Poewe W, Daniel SE. Amyloid ß-peptide and the dementia of Parkinson’s disease. Mov Disord. 1996;11:647–653.

42. Haroutunian V, Serby M, Purohit DP, Perl DP, Marin D, Lantz M, et al.. Contribution of Lewy body inclusions to dementia in patients with and without Alzheimer disease neuropathological conditions. Arch Neurol. 2000;57:1145–1150.

43. McKeith IG. Dementia with Lewy bodies. Br J Psychiatry. 2002;180:144–147.

44. Ala TA, Hughes LF, Kyrouac GA, Ghobrial MW, Elble RJ. The Mini-Mental State exam may help in the differentiation of dementia with Lewy bodies and Alzheimer’s disease. Int J Geriatr Psychiatry. 2002;17:503–509.

45. Horimoto Y, Matsumoto M, Nakazawa H, Yuasa H, Morishita M, Akatsu H, et al.. Cognitive conditions of pathologically confirmed dementia with Lewy bodies and Parkinson’s disease with dementia. J Neurol Sci. 2003;216:105–108.

46. Rockwell E, Choure J, Galasko D, Olichney J, Jeste DV. Psychopathology at initial diagnosis in dementia with Lewy bodies versus Alzheimer disease: comparison of matched groups with autopsy-confirmed diagnoses. Int J Geriatr Psychiatry. 2000;15:819–823.

47. Grace JB, Walker MP, McKeith IG. A comparison of sleep profiles in patients with dementia with Lewy bodies and Alzheimer’s disease. Int J Geriatr Psychiatry. 2000;15:1028–1033.

48. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 10.1a January 2009 [Click to have a look at the home page]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

May  23, 2009 — We’ve cloned sheep, mice, dogs and more. So are humans next

Video 1. Are humans next to clone

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

May 21, 2009 —  Low back pain is the most commonly encountered complaint in a primary care physician’s practice, with lumbar disc degeneration being one of the likeliest etiologies. In fact, degenerative disc disease (DDD) has been touted as the leading cause of pain and dysfunction in the United States, and its socioeconomic impact, with an estimated 50 billion dollars in annual health care costs, has deeply affected the country’s medical resources and productivity as a society today.^[1] Degenerative disc disease results from changes both in the nucleus pulposus and the anulus fibrosis. The number of viable cells in the nucleus pulposus declines as people age. Also the concentration of proteoglycans and water decreases. Additionally, proteoglycans begin to fragment and the composition of the nucleus pulposus becomes progressively more fibrotic. The outer anulus undergoes myxomatous degeneration with loss of normal collagen fiber organization, leading to increased incidence of fissures and cracks.^[2] Ultimately, disc space height is compromised. Disc degeneration is accompanied by both small vessel proliferation and nerve fiber invasion into the vertebral endplates and peripheral regions of the disc. These structural and mechanical changes are believed to be contributing factors to a patient’s back pain. Degenerative disc disease is defined by both the biologic and mechanical degradations of the intervertebral disc that subsequently lead to pain. Degeneration of the disc is confirmed clinically by patient history, physical examination, and radiographic studies. Discography is a useful procedure that can help elucidate which level or levels are involved. Under fluoroscopic guidance, dye is inserted into the disc space, increasing the intradiscal pressure, and provoking a patient’s typical pain if the disc is the pain generator.

Figure 1. A metal artificial disc

Video 1. Lumbar Artificial Disc Replacement (ADR) Surgery

Once the diagnosis of Degenerative disc disease is made, conservative methods such as nonsteroidal anti-inflammatory drugs and a structured physical therapy regimen are employed (for at least 6 months) as the first steps in management. Treatments such as ultrasound, acupuncture, spinal manipulation (chiropractor), muscle relaxants, traction, and shoe orthotics may be used alternatively or additionally, to attempt to alleviate the discomfort. For patients who have failed nonoperative treatment and continue to experience incapacitating axial back pain that severely limits their activities of daily living, the standard of care for Degenerative disc disease in the lumbar spine has been spinal fusion. Reports in the literature, however, demonstrate that spinal fusion alters the biomechanical stresses at the affected level, which may contribute to adjacent level degeneration.^[3,4] Lumbar artificial discs have recently been proposed as an attractive alternative to arthrodesis because they restore or maintain the basic motion of the intervertebral segment, thereby eliminating a potential cause of adjacent segment degeneration.

Video 2. Spinal treatment surgical options with artificial spine disc.. Total Disc Replacement implant provides the possibility for motion by allowing the top endplate to move over the plastic ball attached to the bottom endplate. The materials used in Total Disc Replacement implant have been used in spinal disc replacement for over 20 years in Europe and are the most commonly used materials in knee and hip replacements worldwide.

The gold standard of treatment for Degenerative disc disease causing mechanical back pain in the lumbar spine unresponsive to nonoperative treatment has been fusion. Clinical studies, however, suggest that the altered biomechanical stresses created by fusion contribute to adjacent level degeneration. Recently in the United States, the artificial disc prosthesis has become an attractive option. Its aim is to attempt restoration and preservation of normal spinal biomechanics while withstanding the loads applied by the human body. By restoring normal segmental motion of the spine, the hope is to reduce or even eliminate adjacent level degeneration. Eck et al reviewed biomechanical and radiologic studies after lumbar fusion to examine adjacent segment degeneration after lumbar fusion.^[20] Their evidence showed that true fusion did, in fact, alter the biomechanics at junctional levels, creating increased forces, mobility, and intradiscal pressure in adjacent segments. The altered biomechanics then lead to the Modic changes in the adjacent disc as seen by magnetic resonance imaging and the symptomatic changes as noted by the patients. Gillet reviewed a series of 106 lumbar spinal fusions with a total of 2- to 15-year follow-up and showed a 20% reoperation rate due to this adjacent segment degeneration.^[21] Ghiselli et al had similar results with long-term follow-up of lumbar fusion. In a series of 215 fusions and follow up of over 6 years, there was a 27.4% reoperation rate due to adjacent level disease.^[22] However, the segments close to the fusion are not the only ones susceptible to degeneration. A report by Schlegel et al ^[3] with a patient population of 58 and an average symptom-free period of 13.1 years, found that segments adjacent to the adjacent level of fusion itself were just as likely to break down and cause symptoms possibly requiring revision surgery.

The theoretical advantage of lumbar disc replacement over spine fusion is that the replaced disc would allow motion at the damaged level and would not transfer stresses to adjacent levels. The goal is to achieve the same pain reduction as spinal fusion, but eliminate some of the complications.

Unfortunately, lumbar disc replacement is a new surgery. While it is tempting to accept that this is a “better” treatment (pain reduction with less complications), we do not know if that is really the case. Lumbar disc replacements can break and they can become infected. Furthermore, the metal and plastic can itself wear out causing problems down the road. The question is which treatment offers the best result with the lowest complication rate. The answer, right now, is that we do not know. Lumbar disc replacements have not been performed on enough patients for a long enough time to know what potential problems may arise from this surgery.

Please note

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

May 15, 2009 — The following video discusses the low back pains, which affects as many as two out of three Americans at some point in their lives. Learn the common triggers and new treatment options for this irksome condition.

Video 1. Conservative Management of Low Back Pain