Neurodegenerative Disease Alzheimer’s Disease
Figure 3: Intraneuronal Hyperphosphorylated Tau, Antibody AT8, Magnification x200
pathologies are frequent in patients with suspected NPH. In addition to these, vascular changes and non-specific findings such as gliosis and meningeal thickening, have been observed. It is noteworthy that by applying currently used techniques, no changes specific for NPH have been observed.
Figure 4: Positive Staining by Antibody p62, Magnification x400
Despite the fact that biopsy samples are small in size and from only a single region of the brain, according to autopsy studies the frontal cortex is a fairly representative location to evaluate Aβ deposits in AD.4 However, HPτ depositions especially in the early phase may escape the small frontal cortical samples since they usually begin to accumulate in the medial temporal lobe and olfactory bulb. Still further studies correlating brain biopsy and post-mortem findings are needed to validate the clinical significance of the surgically obtained frontal cortical biopsy in diagnostics of dementia. From the 433 patients in our series, 253 died, but only 10 had had a full neuropathological examination of the brain. Three of these cases had displayed Aβ aggregates in the biopsy specimen and all of them displayed Aβ pathology later in the post mortem specimen. Interestingly, the final stage Aβ pathologies were quite prominent reaching Thal phases 4 to 5. Furthermore, all 10 cases displayed Aβ pathology in post mortem study and in two cases the Aβ pathology had reached Thal phase 3 even if nothing was seen at biopsy, although with nearly six years delay.38
Methodological Aspects Biopsy Procedure
Standardised location for biopsy is essential. For detection of cortical AD pathology (Aβ) right (non-dominant) prefrontal area 2–3 cm from the midline in front of the coronal suture of the skull is considered to be ideal. This is also the standard puncture site of intraventricular catheters. Image guided (navigated) technique is preferable to optimise the site of interest if the standardised location is not used or lesion detectable by imaging methods is the primary target.
A standard 12 mm burr hole made under local anaesthesia and sedation allows large enough exposure to the cerebral cortex (an even smaller hole can be made with a biopsy needle). In case of a cortical vein in the site of the initial burr hole, an enlargement or even second burr hole might be needed. Avoidance of any injury to cortical veins is compulsory to avoid potential complications.
should be noted that only a subset of patients with Aβ alone finally developed clinical AD. On the other hand, the median follow-up time was restricted to 4.4 years owing to substantial mortality and when the patients with clinical AD were excluded the Aβ alone or together with HPτ did not predict other types of dementia. These findings together support the concept of amyloid accumulation as preceding phenomenon of clinical AD.
A study using silver stain methods that are less sensitive than immunohistochemistry (IHC) techniques has reported that 35 of 56 patients (63 %) with cognitive impairment and suspected NPH displayed AD-related pathology in frontal brain biopsy, i.e., neuritic/diffuse plaques.36
with NPH had AD-related tangles and plaques and 12 (43 %) of the 28 patients with adequate follow-up developed clinical AD.37
These
studies are not fully comparable owing to different patient selection criteria and methodology, but clearly indicate that AD-related
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Biopsy can be performed using small forceps preferably with a small surgical (dura) knife avoiding the crushing of the tissue. The easiest way to obtain a standard biopsy is a cutting biopsy needle (at least 14 Gauge [G]) giving 1–2 x 5–10 mm cylindrical transcortical samples with underlying white matter (see Figure 1). When the primary indication of the surgical procedure is biopsy, e.g. in progressive dementia with an undefined origin, a larger sample is usually needed, by less invasive diagnostic methods .
Processing of the Sample In another report 10 (26 %) out of 38 patients
Ideally the fresh sample is transferred directly to the pathology laboratory with as short delay as possible (less than 60 minutes). Thus, the sample can be processed by a pathologist, divided into paraffin block and fresh frozen sample (cortex and white matter in different tubes). A formalin fixed (FF) sample alone is sufficient if only haematoxylin-eosin (HE), silver and IHC methods are going to be used. For special research purposes immediately (e.g. in an operating theatre) frozen samples might be considered.
EUROPEAN NEUROLOGICAL REVIEW
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